肉牛PPARs家族和PLIN基因遗传变异及其与秦川牛胴体、肉质性状相关分析
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摘要
本研究以秦川牛、南阳牛、鲁西牛、郏县红牛、夏南牛以及安格斯牛6个肉用品种共计717个个体为实验动物,利用PCR-SSCP、DNA测序技术及DNA序列分析技术,研究了影响牛脂肪代谢的4个基因(PPARα、PPARδ、PPARγ以及PLIN)的遗传变异,分析了其遗传结构和遗传多样性。并对108头秦川牛在上述位点的多样性与其胴体、肉质性状进行了相关分析,同时利用生物信息学分析了部分分子标记的作用机理,以期筛选出对肉牛重要经济性状具有显著效应的功能基因或分子标记,为肉牛的高效选育和分子标记数据库的建立、种质资源保存与利用提供遗传学依据。本研究主要获得了以下结果: 1. PPARα基因多态性及其与秦川牛胴体、肉质性状的相关分析
采用PCR-SSCP及DNA测序方法,共研究了6个群体PPARα基因的8个基因座,包括PPARα基因的7个外显子及第2内含子。发现了6个新的SNP位点。
在PPARα基因的第2内含子检测到3个SNP位点,分别为2666 C>G,2678 T>C和2706 T>C的突变,在该基因座,D等位基因占主导地位,秦川牛、南阳牛、郏县红牛、鲁西牛、夏南牛和安格斯牛等位基因D的频率分别为,0.571、0.404、0.419、0.417、0.422和0.386;PIC值分别为0.421、0.416、0.434、0.447、0.438和0.413,均为中度多态,遗传多态性丰富。该位点与眼肌面积极显著相关(P<0.01),表现为CC基因型个体眼肌面积极显著高于CD基因型个体(P<0.01)。
PCR-SSCP检测到在第5外显子的138bp处存在一个T>C的突变,该突变发生在第5外显子和第5内含子的交界处。未引起氨基酸的变化。秦川牛和夏南牛群体处于Hardy-Weinberg不平衡状态(P<0.05),南阳牛、郏县红牛、安格斯和鲁西牛群体处于Hardy-Weinberg平衡状态(P>0.05)。同时这6个牛群体均属于中度多态,遗传多态性丰富程度从大到小依次为秦川牛、郏县红牛、安格斯牛、鲁西牛、夏南牛和南阳牛。138T>C位点与秦川牛的眼肌面积、背膘厚和系水力指标具有相关性。
184 C>T突变发生于PPARα基因的第7外显子上,在该位点,秦川牛和安格斯这2个群体处于Hardy-Weinberg非平衡状态(P<0.05),南阳牛、郏县红牛、夏南牛和鲁西牛群体处于Hardy-Weinberg平衡状态(P>0.05)。遗传学指标结果显示:秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛群体属于低度多态,南阳牛属于中度多态。该位点与秦川牛背膘厚和胴体长显著相关(P<0.05)。
260 C>T突变发生在PPARα基因的第8外显子上,在南阳牛、秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛中,等位基因G/H的频率分别为0.925/0.075、0.864/0.136、0.791/0.209、0.828/0.172、0.835/0.165和0.853/0.147。在南阳牛群体中未检测到基因型HH。该位点GG基因型为优势基因型,等位基因G为优势等位基因。南阳牛处于Hardy-Weinberg平衡状态(P>0.05),秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛5个群体均处于Hardy-Weinberg不平衡状态(P<0.05)。郏县红牛属于中度多态,南阳牛、秦川牛、安格斯、鲁西牛和夏南牛这5个群体均属于低度多态。260 C>T位点与系水力指标显著相关(P<0.05),在秦川牛群体中,GG基因型个体在系水力性状方面显著高于GH基因型个体(P<0.05)。
2. PPARδ基因多态性及其与秦川牛胴体、肉质性状的相关分析
本研究对PPARδ基因的7个外显子进行SNP检测,结果仅发现了1个SNP位点,该突变发生在第2内含子,为61 C>T突变。在检测的6个群体中,均表现为KK基因型占主导地位,等位基因K为优势等位基因。南阳牛和夏南牛处于Hardy-Weinberg平衡状态( P>0.05 ),秦川牛、安格斯、鲁西牛和郏县红牛群体均处于Hardy-Weinberg不平衡状态( P<0.05 )。夏南牛群体遗传多态性较丰富,为中度多态,其余5个群体均属于低度多态。PPARδ基因61 C>T多态位点与秦川牛宰前活重和胴体重显著相关,表现为KK基因型个体宰前活重显著高于KL和LL基因型个体( P<0.05 ),KK基因型个体胴体长显著高于KL基因型个体。
3. PPARγ基因多态性及其与秦川牛胴体、肉质性状的相关分析
利用PCR-SSCP和DNA测序法对PPARγ基因的7个外显子及部分5’调控区进行了SNP筛查。4个新的SNP位点被发现,分别为外显子1的200 A>G,内含子2的59 C>G,外显子5的62 C>T,外显子7的74 G>T突变。
PPARγ基因A>G多态位点位于第一外显子的200bp处,该位点导致天冬氨酸(D)转变为甘氨酸(G)。在南阳牛、秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛6个群体中,等位基因A/B的频率分别为0.81/0.19、0.86/0.14、0.80/0.20、0.76/0.24、0.72/0.28和0.87/0.13。安格斯群体处于Hardy-Weinberg非平衡状态(P<0.05),其余5个群体均处于Hardy-Weinberg平衡状态(P>0.05)。秦川牛和夏南牛属于低度多态,南阳牛、郏县红牛、安格斯和鲁西牛属于中度多态。200 A>G位点与背膘厚及背部皮下脂肪厚显著相关,表现为AA基因型个体背膘厚和背部皮下脂肪厚显著高于AB基因型个体(P<0.05)。生物信息学研究发现,天冬氨酸转变为甘氨酸后,导致蛋白的二级结构在该处出现一个α螺旋的丢失,并且无规则卷曲变大。碱基突变导致该基因氨基酸疏水性增大,松散度减小。这些变化可能与该基因功能的变化有关。
59C>G突变位于PPARγ基因第2内含子上,是在检测PPARγ基因第2外显子的突变时候发现的。该位点Y等位基因占主导地位,南阳牛、秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛6个群体均处于Hardy-Weinberg不平衡状态(P<0.05)。南阳牛、郏县红牛、安格斯、鲁西牛和夏南牛5个群体属于中度多态,遗传多态性较丰富,秦川牛遗传多态性较低,为低度多态。并且研究发现该位点与秦川牛的背部皮下脂肪厚之间存在显著相关性。
62C>T多态位点发生在PPARγ基因第5外显子上,6个群体均表现为II基因型的缺失,在南阳牛、秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛6个群体中,等位基因J/I的频率分别为0.94/0.06、0.87/0.13、0.90/0.10、0.90/0.10、0.91/0.09和0.94/0.04。其中仅秦川牛处于Hardy-Weinberg不平衡状态(P<0.05),6个群体均表现为低度多态。相关性分析结果显示:JJ基因型的个体的背部皮下脂肪厚指标显著高于JI基因型个体(P<0.05)。
74G>T位点导致了编码氨基酸由谷氨酰胺(Q)突变为组氨酸(H),生物信息学研究发现,氨基酸的突变导致该处一个β转角的丢失,无规则卷曲变小。疏水性增大,松散度细微减少。南阳牛、郏县红牛、秦川牛和鲁西牛群体处于Hardy-Weinberg平衡状态(P>0.05) ,安格斯和夏南牛群体处于Hardy-Weinberg不平衡状态(P<0.05)。南阳牛和夏南牛属于低度多态,其余4个群体属于中度多态。相关性分析结果显示:OP基因型个体胴体长显著高于OO和PP基因型个体(P<0.05),OO基因型个体背膘厚指标显著高于OP基因型个体(P<0.05),极显著高于PP基因型个体(P<0.01),OO基因型个体系水力显著低于OP和PP基因型个体(P<0.05)。
4. PLIN基因多态性及其与秦川牛胴体、肉质性状的相关分析
在牛PLIN基因的4个基因座首次检测到2处突变,分别为外显子3的156 T>C突变,外显子4的14 C>T突变。这2个位点在秦川牛群体中均处于中度多态,在156 T>C位点,AB基因型个体的宰前活体质量、胴体质量、背膘厚和眼肌面积均高于AA和BB基因型个体(P<0.05),而且AB基因型个体与AA基因型个体相比,在宰前活体质量、胴体质量、背膘厚和眼肌面积这4个指标方面达到差异极显著水平(P<0.01)。14 C>T突变相关性分析结果显示:DE基因型个体的胴体长、胴体胸深以及背膘厚显著高于DD和EE基因型个体(P<0.05),同时DD基因型个体肌肉嫩度极显著低于EE和DE基因型个体(P<0.01)。
Genetic variations of lipid metabolism related genes (PPARα, PPARδ, PPARγ, and PLIN) were detected by PCR-SSCP, DNA sequencing and DNA sequence analysis in 717 individuals of six populations (Nanyang, Qinchuan, Jiaxian Red cattle, Luxi, Angus, and Xianan), and association analysis were carried out to evaluate the effects of genotypes of candidate genes on carcass and meat quality traits of 108 Qinchuan cattle. Molecular markers function was analyzed by bioinformation in missense mutation loci. The object of this study were to discover the hereditary characteristics and to explore molecular markers with significant effects on economic important traits for efficient selection and improvement of Chinese cattle, and to provide genetic information for foundation of molecular marker database, protection and usage of breed resource of Chinese cattle. The results were as follows:
1. Relationship between genetic variation of PPARαgene and carcass, meat quality traits in Qinchuan cattle
The variations of eight loci in PPARαgene, including seven exons and intron2, were detected in six populations using PCR-SSCP and DNA sequencing. Six SNPs were detected for the first time.
Three SNPs (2666 C>G, 2678 T>C, 2706 T>C) were detected, which located at the intron2 of PPARαgene. Allele gene D was predominant in the locus. The allele frequencies of D in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi, Xianan and Augus populations were 0.571, 0.404, 0.419, 0.417, 0.422 and 0.386. And in the six populations, the SNP was moderate polymorphic, the PIC values were 0.421, 0.416, 0.434, 0.447, 0.438 and 0.413, respectively. The 2666 C>G locus was high significantly with loin muscle area (P<0.01), individuals with genotype CC had higher loin muscle area than those with genotype CD (P<0.01).
T>C mutation was detected in the exon5 of PPARαgene by PCR-SSCP, which located at the juncture of exon5 and intron5, and the locus was synonymous mutation. The Chi-Square tests showed Nanyang, Jiaxian Red cattle, Augus, and Luxi cattle populations were at Hardy-Weinberg equilibrium (P>0.05), but Qinchuan cattle and Xianan cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). The locus was moderate polymorphic in six populations, therefore the genetic polymorphisms from higher to lower were Qinchuan cattle, Jiaxian Red cattle, Augus, Luxi, Xianan and nanyang cattle. The 138T>C SNP had significant effects on loci muscle area, back fat thickness and hold water capability in Qinchuan cattle population.
184 C>T mutation located at the seventh exon of PPARαgene. In this locus, Nanyang, Jiaxian Red cattle, Xianan, and Luxi cattle populations were at Hardy-Weinberg equilibrium (P>0.05), but Qinchuan cattle and Augus cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). The index of genetics showed that Qinchuan cattle, Jiaxian Red cattle, Augus, Luxi and Xianan cattle populations belonged to low polymorphic and Nanyang cattle population was moderate polymorphic. The 184 C>T SNP was significantly associated with back fat thickness and carcass length (P<0.05).
260 C>T mutation was detected in the eighth exon of PPARαgene. The allele frequencies of G/H were 0.925/0.075, 0.864/0.136, 0.791/0.209, 0.828/0.172, 0.835/0.165 and 0.853/0.147 in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi, Xianan and Augus populations. Genotype II was no detected in Nanyang cattle population. And genotype GG was predominant, the frequencies of allele G was the highest in this locus. Nanyang cattle population was at Hardy-Weinberg equilibrium (P>0.05), but Qinchuan cattle, Jiaxian Red cattle, Augus, Luxi and Xianan cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). Except for Jiaxian Red cattle (0.25T SNP was significantly associated with hold water capability (P<0.05). Individuals with genotype GG had higher hold water capability than those with genotype GH (P<0.05).
2. Relationship between genetic variation of PPARδgene and carcass, meat quality traits in Qinchuan cattle
The seventh exons were detected, and only one SNP (61 C>T) was found in the intron2 in the PPARδgene. Genotype KK and allele K were predominant in the six populations. Nanyang and Xianan cattle populations were at Hardy-Weinberg equilibrium (P>0.05), but Qinchuan cattle, Jiaxian Red cattle, Augus and Luxi cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). The 61 C>T SNP was moderate polymorphic in Xianan population, was low polymorphic in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi and Augus populations. The 61 C>T SNP was significantly associated with Slaughter weight and Carcass weight (P<0.05) in Qinchuan cattle. Animals with genotype KK had higher Slaughter weight than those with genotypes KL and LL (P<0.05), individuals with genotype KK had higher carcass weight than those with genotype KL (P<0.05).
3. Relationship between genetic variation of PPARγgene and carcass, meat quality traits in Qinchuan cattle
Four SNPs (200 A>G (exon1), 59 C>G (intron2), 62 C>T (exon5) and 74 G>T (exon7)) of PPARγgene were detected in 8 loci, which located coding region and the part of 5'control region by PCR-SSCP and DNA sequencing.
A>G SNP was detected, which located at 200 bp in the first exon of PPARγgene and resulted in D7G change. The allele frequencies of A/B were 0.81/0.19, 0.86/0.14, 0.80/0.20, 0.76/0.24, 0.72/0.28 and 0.87/0.13 in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi, Xianan and Augus populations. In the six populations, Augus population was at Hardy-Weinberg disequilibrium (P<0.05). In Qinchuan cattle and Xianan cattle populations, the SNP was low polymorphic, but in Nanyang, Jiaxian Red cattle, Augus and Luxi cattle populaions, the SNP was moderate polymorphic. The 200 A>G SNP was significantly associated with back fat thickness and back subcutaneous fat thickness. Individuals with genotype AA had high back fat thickness and back subcutaneous fat thickness than those with genotype AB (P<0.05). Bioinformatics analysis showed that the mutation led Asp change into Gly, which had theα-helix lost, the coil wax, the hydrophobicity increase and loose degree decrease. This change may be related to the change of gene function.
The 59 C>G SNP produced at intron2 of PPARγgene, which was found when detected the SNP of exon2. Allele Y was dominant in the six populations, all populations were at Hardy-Weinberg disequilibrium (P<0.05). In Nanyang, Jiaxian Red cattle, Augus, Luxi and Xianan cattle populations, the SNP was moderate polymorphic, but in Qinchuan cattle population, the SNP was low polymorphic. The 59 C>G SNP was had significant effects on back subcutaneous fat thickness.
62 C>T mutation located at exon5 of PPARγgene, six populations all displayed the lost of genotype II. The allele frequencies of J/I were 0.94/0.06, 0.87/0.13, 0.90/0.10, 0.90/0.10, 0.91/0.09 and 0.94/0.04 in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi, Xianan and Augus populations. Only Qinchuan cattle was at Hardy-Weinberg disequilibrium (P<0.05). All populations were at low polymorphic. Correlation analysis showed individuals with genotype JJ had higher back subcutaneous fat thickness than those with genotype JI (P<0.05).
The 74 G>T mutation resulted Glu change into His. Bioinformatics analysis revealed there had theβ-sheet lost and coil decreased in 2D structure, and the hydrophobicity increased and loose degree decreased in the locus. Qinchuan cattle, Jiaxian Red cattle, Augus, Luxi and Nanyang cattle populations were at Hardy-Weinberg equilibrium (P>0.05), but Angus and Xianan cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). In Nanyang cattle and Xianan cattle populations, the SNP was low polymorphic, in other populations, the SNP was moderate polymorphic. Animal with genotype OP was higher carcass length than those with genotypes OO and PP (P<0.05), individuals with genotype OO was higher mean values than these with genotypes OP (P<0.05) and PP (P<0.01) for back fat thickness, and animals with genotype OO was lower mean values than these with genotypes OP and PP (P<0.05) for hold water capability.
4. Relationship between genetic variation of PLIN gene and carcass, meat quality traits in Qinchuan cattle
A total of two SNPs (156 T>C (exon3), 14 C>T (exon4)) of PLIN gene were detected in 4 loci in Qinchuan cattle population. The two SNPs were belonging to moderate polymorphic. In the 156 T>C locus, animal with genotype AB was higher slaughter weight, carcass weight, back fat thickness and loin muscle area than those with genotypes AA and BB, and compared to individual with AA genotype was very significantly different(P<0.01). In the 14 C>T locus, this analysis also showed that the carcass length, carcass chest depth and back fat thickness of individual with DE genotype was significant higher than those with EE and DD genotypes (P<0.05), and compared to individual with EE and DE genotypes, the tenderness of individual with DD genotype was very significantly different(P<0.01).
采用PCR-SSCP及DNA测序方法,共研究了6个群体PPARα基因的8个基因座,包括PPARα基因的7个外显子及第2内含子。发现了6个新的SNP位点。
在PPARα基因的第2内含子检测到3个SNP位点,分别为2666 C>G,2678 T>C和2706 T>C的突变,在该基因座,D等位基因占主导地位,秦川牛、南阳牛、郏县红牛、鲁西牛、夏南牛和安格斯牛等位基因D的频率分别为,0.571、0.404、0.419、0.417、0.422和0.386;PIC值分别为0.421、0.416、0.434、0.447、0.438和0.413,均为中度多态,遗传多态性丰富。该位点与眼肌面积极显著相关(P<0.01),表现为CC基因型个体眼肌面积极显著高于CD基因型个体(P<0.01)。
PCR-SSCP检测到在第5外显子的138bp处存在一个T>C的突变,该突变发生在第5外显子和第5内含子的交界处。未引起氨基酸的变化。秦川牛和夏南牛群体处于Hardy-Weinberg不平衡状态(P<0.05),南阳牛、郏县红牛、安格斯和鲁西牛群体处于Hardy-Weinberg平衡状态(P>0.05)。同时这6个牛群体均属于中度多态,遗传多态性丰富程度从大到小依次为秦川牛、郏县红牛、安格斯牛、鲁西牛、夏南牛和南阳牛。138T>C位点与秦川牛的眼肌面积、背膘厚和系水力指标具有相关性。
184 C>T突变发生于PPARα基因的第7外显子上,在该位点,秦川牛和安格斯这2个群体处于Hardy-Weinberg非平衡状态(P<0.05),南阳牛、郏县红牛、夏南牛和鲁西牛群体处于Hardy-Weinberg平衡状态(P>0.05)。遗传学指标结果显示:秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛群体属于低度多态,南阳牛属于中度多态。该位点与秦川牛背膘厚和胴体长显著相关(P<0.05)。
260 C>T突变发生在PPARα基因的第8外显子上,在南阳牛、秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛中,等位基因G/H的频率分别为0.925/0.075、0.864/0.136、0.791/0.209、0.828/0.172、0.835/0.165和0.853/0.147。在南阳牛群体中未检测到基因型HH。该位点GG基因型为优势基因型,等位基因G为优势等位基因。南阳牛处于Hardy-Weinberg平衡状态(P>0.05),秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛5个群体均处于Hardy-Weinberg不平衡状态(P<0.05)。郏县红牛属于中度多态,南阳牛、秦川牛、安格斯、鲁西牛和夏南牛这5个群体均属于低度多态。260 C>T位点与系水力指标显著相关(P<0.05),在秦川牛群体中,GG基因型个体在系水力性状方面显著高于GH基因型个体(P<0.05)。
2. PPARδ基因多态性及其与秦川牛胴体、肉质性状的相关分析
本研究对PPARδ基因的7个外显子进行SNP检测,结果仅发现了1个SNP位点,该突变发生在第2内含子,为61 C>T突变。在检测的6个群体中,均表现为KK基因型占主导地位,等位基因K为优势等位基因。南阳牛和夏南牛处于Hardy-Weinberg平衡状态( P>0.05 ),秦川牛、安格斯、鲁西牛和郏县红牛群体均处于Hardy-Weinberg不平衡状态( P<0.05 )。夏南牛群体遗传多态性较丰富,为中度多态,其余5个群体均属于低度多态。PPARδ基因61 C>T多态位点与秦川牛宰前活重和胴体重显著相关,表现为KK基因型个体宰前活重显著高于KL和LL基因型个体( P<0.05 ),KK基因型个体胴体长显著高于KL基因型个体。
3. PPARγ基因多态性及其与秦川牛胴体、肉质性状的相关分析
利用PCR-SSCP和DNA测序法对PPARγ基因的7个外显子及部分5’调控区进行了SNP筛查。4个新的SNP位点被发现,分别为外显子1的200 A>G,内含子2的59 C>G,外显子5的62 C>T,外显子7的74 G>T突变。
PPARγ基因A>G多态位点位于第一外显子的200bp处,该位点导致天冬氨酸(D)转变为甘氨酸(G)。在南阳牛、秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛6个群体中,等位基因A/B的频率分别为0.81/0.19、0.86/0.14、0.80/0.20、0.76/0.24、0.72/0.28和0.87/0.13。安格斯群体处于Hardy-Weinberg非平衡状态(P<0.05),其余5个群体均处于Hardy-Weinberg平衡状态(P>0.05)。秦川牛和夏南牛属于低度多态,南阳牛、郏县红牛、安格斯和鲁西牛属于中度多态。200 A>G位点与背膘厚及背部皮下脂肪厚显著相关,表现为AA基因型个体背膘厚和背部皮下脂肪厚显著高于AB基因型个体(P<0.05)。生物信息学研究发现,天冬氨酸转变为甘氨酸后,导致蛋白的二级结构在该处出现一个α螺旋的丢失,并且无规则卷曲变大。碱基突变导致该基因氨基酸疏水性增大,松散度减小。这些变化可能与该基因功能的变化有关。
59C>G突变位于PPARγ基因第2内含子上,是在检测PPARγ基因第2外显子的突变时候发现的。该位点Y等位基因占主导地位,南阳牛、秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛6个群体均处于Hardy-Weinberg不平衡状态(P<0.05)。南阳牛、郏县红牛、安格斯、鲁西牛和夏南牛5个群体属于中度多态,遗传多态性较丰富,秦川牛遗传多态性较低,为低度多态。并且研究发现该位点与秦川牛的背部皮下脂肪厚之间存在显著相关性。
62C>T多态位点发生在PPARγ基因第5外显子上,6个群体均表现为II基因型的缺失,在南阳牛、秦川牛、郏县红牛、安格斯、鲁西牛和夏南牛6个群体中,等位基因J/I的频率分别为0.94/0.06、0.87/0.13、0.90/0.10、0.90/0.10、0.91/0.09和0.94/0.04。其中仅秦川牛处于Hardy-Weinberg不平衡状态(P<0.05),6个群体均表现为低度多态。相关性分析结果显示:JJ基因型的个体的背部皮下脂肪厚指标显著高于JI基因型个体(P<0.05)。
74G>T位点导致了编码氨基酸由谷氨酰胺(Q)突变为组氨酸(H),生物信息学研究发现,氨基酸的突变导致该处一个β转角的丢失,无规则卷曲变小。疏水性增大,松散度细微减少。南阳牛、郏县红牛、秦川牛和鲁西牛群体处于Hardy-Weinberg平衡状态(P>0.05) ,安格斯和夏南牛群体处于Hardy-Weinberg不平衡状态(P<0.05)。南阳牛和夏南牛属于低度多态,其余4个群体属于中度多态。相关性分析结果显示:OP基因型个体胴体长显著高于OO和PP基因型个体(P<0.05),OO基因型个体背膘厚指标显著高于OP基因型个体(P<0.05),极显著高于PP基因型个体(P<0.01),OO基因型个体系水力显著低于OP和PP基因型个体(P<0.05)。
4. PLIN基因多态性及其与秦川牛胴体、肉质性状的相关分析
在牛PLIN基因的4个基因座首次检测到2处突变,分别为外显子3的156 T>C突变,外显子4的14 C>T突变。这2个位点在秦川牛群体中均处于中度多态,在156 T>C位点,AB基因型个体的宰前活体质量、胴体质量、背膘厚和眼肌面积均高于AA和BB基因型个体(P<0.05),而且AB基因型个体与AA基因型个体相比,在宰前活体质量、胴体质量、背膘厚和眼肌面积这4个指标方面达到差异极显著水平(P<0.01)。14 C>T突变相关性分析结果显示:DE基因型个体的胴体长、胴体胸深以及背膘厚显著高于DD和EE基因型个体(P<0.05),同时DD基因型个体肌肉嫩度极显著低于EE和DE基因型个体(P<0.01)。
Genetic variations of lipid metabolism related genes (PPARα, PPARδ, PPARγ, and PLIN) were detected by PCR-SSCP, DNA sequencing and DNA sequence analysis in 717 individuals of six populations (Nanyang, Qinchuan, Jiaxian Red cattle, Luxi, Angus, and Xianan), and association analysis were carried out to evaluate the effects of genotypes of candidate genes on carcass and meat quality traits of 108 Qinchuan cattle. Molecular markers function was analyzed by bioinformation in missense mutation loci. The object of this study were to discover the hereditary characteristics and to explore molecular markers with significant effects on economic important traits for efficient selection and improvement of Chinese cattle, and to provide genetic information for foundation of molecular marker database, protection and usage of breed resource of Chinese cattle. The results were as follows:
1. Relationship between genetic variation of PPARαgene and carcass, meat quality traits in Qinchuan cattle
The variations of eight loci in PPARαgene, including seven exons and intron2, were detected in six populations using PCR-SSCP and DNA sequencing. Six SNPs were detected for the first time.
Three SNPs (2666 C>G, 2678 T>C, 2706 T>C) were detected, which located at the intron2 of PPARαgene. Allele gene D was predominant in the locus. The allele frequencies of D in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi, Xianan and Augus populations were 0.571, 0.404, 0.419, 0.417, 0.422 and 0.386. And in the six populations, the SNP was moderate polymorphic, the PIC values were 0.421, 0.416, 0.434, 0.447, 0.438 and 0.413, respectively. The 2666 C>G locus was high significantly with loin muscle area (P<0.01), individuals with genotype CC had higher loin muscle area than those with genotype CD (P<0.01).
T>C mutation was detected in the exon5 of PPARαgene by PCR-SSCP, which located at the juncture of exon5 and intron5, and the locus was synonymous mutation. The Chi-Square tests showed Nanyang, Jiaxian Red cattle, Augus, and Luxi cattle populations were at Hardy-Weinberg equilibrium (P>0.05), but Qinchuan cattle and Xianan cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). The locus was moderate polymorphic in six populations, therefore the genetic polymorphisms from higher to lower were Qinchuan cattle, Jiaxian Red cattle, Augus, Luxi, Xianan and nanyang cattle. The 138T>C SNP had significant effects on loci muscle area, back fat thickness and hold water capability in Qinchuan cattle population.
184 C>T mutation located at the seventh exon of PPARαgene. In this locus, Nanyang, Jiaxian Red cattle, Xianan, and Luxi cattle populations were at Hardy-Weinberg equilibrium (P>0.05), but Qinchuan cattle and Augus cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). The index of genetics showed that Qinchuan cattle, Jiaxian Red cattle, Augus, Luxi and Xianan cattle populations belonged to low polymorphic and Nanyang cattle population was moderate polymorphic. The 184 C>T SNP was significantly associated with back fat thickness and carcass length (P<0.05).
260 C>T mutation was detected in the eighth exon of PPARαgene. The allele frequencies of G/H were 0.925/0.075, 0.864/0.136, 0.791/0.209, 0.828/0.172, 0.835/0.165 and 0.853/0.147 in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi, Xianan and Augus populations. Genotype II was no detected in Nanyang cattle population. And genotype GG was predominant, the frequencies of allele G was the highest in this locus. Nanyang cattle population was at Hardy-Weinberg equilibrium (P>0.05), but Qinchuan cattle, Jiaxian Red cattle, Augus, Luxi and Xianan cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). Except for Jiaxian Red cattle (0.25
2. Relationship between genetic variation of PPARδgene and carcass, meat quality traits in Qinchuan cattle
The seventh exons were detected, and only one SNP (61 C>T) was found in the intron2 in the PPARδgene. Genotype KK and allele K were predominant in the six populations. Nanyang and Xianan cattle populations were at Hardy-Weinberg equilibrium (P>0.05), but Qinchuan cattle, Jiaxian Red cattle, Augus and Luxi cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). The 61 C>T SNP was moderate polymorphic in Xianan population, was low polymorphic in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi and Augus populations. The 61 C>T SNP was significantly associated with Slaughter weight and Carcass weight (P<0.05) in Qinchuan cattle. Animals with genotype KK had higher Slaughter weight than those with genotypes KL and LL (P<0.05), individuals with genotype KK had higher carcass weight than those with genotype KL (P<0.05).
3. Relationship between genetic variation of PPARγgene and carcass, meat quality traits in Qinchuan cattle
Four SNPs (200 A>G (exon1), 59 C>G (intron2), 62 C>T (exon5) and 74 G>T (exon7)) of PPARγgene were detected in 8 loci, which located coding region and the part of 5'control region by PCR-SSCP and DNA sequencing.
A>G SNP was detected, which located at 200 bp in the first exon of PPARγgene and resulted in D7G change. The allele frequencies of A/B were 0.81/0.19, 0.86/0.14, 0.80/0.20, 0.76/0.24, 0.72/0.28 and 0.87/0.13 in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi, Xianan and Augus populations. In the six populations, Augus population was at Hardy-Weinberg disequilibrium (P<0.05). In Qinchuan cattle and Xianan cattle populations, the SNP was low polymorphic, but in Nanyang, Jiaxian Red cattle, Augus and Luxi cattle populaions, the SNP was moderate polymorphic. The 200 A>G SNP was significantly associated with back fat thickness and back subcutaneous fat thickness. Individuals with genotype AA had high back fat thickness and back subcutaneous fat thickness than those with genotype AB (P<0.05). Bioinformatics analysis showed that the mutation led Asp change into Gly, which had theα-helix lost, the coil wax, the hydrophobicity increase and loose degree decrease. This change may be related to the change of gene function.
The 59 C>G SNP produced at intron2 of PPARγgene, which was found when detected the SNP of exon2. Allele Y was dominant in the six populations, all populations were at Hardy-Weinberg disequilibrium (P<0.05). In Nanyang, Jiaxian Red cattle, Augus, Luxi and Xianan cattle populations, the SNP was moderate polymorphic, but in Qinchuan cattle population, the SNP was low polymorphic. The 59 C>G SNP was had significant effects on back subcutaneous fat thickness.
62 C>T mutation located at exon5 of PPARγgene, six populations all displayed the lost of genotype II. The allele frequencies of J/I were 0.94/0.06, 0.87/0.13, 0.90/0.10, 0.90/0.10, 0.91/0.09 and 0.94/0.04 in Qinchuan, Nanyang, Jiaxian Red cattle, Luxi, Xianan and Augus populations. Only Qinchuan cattle was at Hardy-Weinberg disequilibrium (P<0.05). All populations were at low polymorphic. Correlation analysis showed individuals with genotype JJ had higher back subcutaneous fat thickness than those with genotype JI (P<0.05).
The 74 G>T mutation resulted Glu change into His. Bioinformatics analysis revealed there had theβ-sheet lost and coil decreased in 2D structure, and the hydrophobicity increased and loose degree decreased in the locus. Qinchuan cattle, Jiaxian Red cattle, Augus, Luxi and Nanyang cattle populations were at Hardy-Weinberg equilibrium (P>0.05), but Angus and Xianan cattle populations were at Hardy-Weinberg disequilibrium (P<0.05). In Nanyang cattle and Xianan cattle populations, the SNP was low polymorphic, in other populations, the SNP was moderate polymorphic. Animal with genotype OP was higher carcass length than those with genotypes OO and PP (P<0.05), individuals with genotype OO was higher mean values than these with genotypes OP (P<0.05) and PP (P<0.01) for back fat thickness, and animals with genotype OO was lower mean values than these with genotypes OP and PP (P<0.05) for hold water capability.
4. Relationship between genetic variation of PLIN gene and carcass, meat quality traits in Qinchuan cattle
A total of two SNPs (156 T>C (exon3), 14 C>T (exon4)) of PLIN gene were detected in 4 loci in Qinchuan cattle population. The two SNPs were belonging to moderate polymorphic. In the 156 T>C locus, animal with genotype AB was higher slaughter weight, carcass weight, back fat thickness and loin muscle area than those with genotypes AA and BB, and compared to individual with AA genotype was very significantly different(P<0.01). In the 14 C>T locus, this analysis also showed that the carcass length, carcass chest depth and back fat thickness of individual with DE genotype was significant higher than those with EE and DD genotypes (P<0.05), and compared to individual with EE and DE genotypes, the tenderness of individual with DD genotype was very significantly different(P<0.01).
引文
陈娜,吴英良. 2006. PPARδ的结构及其生物学功能与疾病[J].中国药理学通报, 22(9):1035~1038.
陈雪香,刘合焜. 2008. PPARα基因多态性与2型糖尿病关系研究[J].医学综述, 14(6): 897~899.
邓其兰,余冰,陈代文. 2009.围脂滴蛋白(Perlipin)在脂质代谢中的功能[J].饲料工业, 30(5): 8~9.
胡承,贾伟平,方启晨,张蓉,王从容,陆俊茜,项坤三. 2005. PPARδ87T→C基因多态性与代谢综合征的关联研究[J].中华内分泌代谢杂志, 21: 380~383.
孔保华,陶菲,刁新平. 2002.中国肉牛产业的现状和发展趋势[J].肉类研究, 1: 10~13.
孔路军,王爱国,傅金恋,张毅良,王晓凤. 2006.猪PPARs基因组织表达特性的研究[J].遗传育种, 42(19):1~4
李昕. 2006. PPARγ及apM1基因多态性与多囊卵巢综合征肥胖异质性的相关研究[博士学位论文].上海:复旦大学.
罗锦标,田勇,陶争荣,袁青,李国勤,王德前,原爱平,邹丽丽,卢立志,沈军达,石放雄. 2008. PPAR基因在鹅肥肝形成中的可调节性表达[J].中国农业科学, 41(10): 3270~3276.
孟和,李辉,王宇祥. 2004.鸡PPARs基因组织表达特性的研究[J].遗传学报, 31(7): 682~687.
戚晓红,张昭萍,李晓宇,阕玲俐,吴翠贞. 2003.过氧化物酶体增殖物激活受体在实验性大鼠脂肪肝中的表达[J].中国病理生理杂志, 19(9) : 1206~1209.
石如玲,姜玲玲. 2005.胆汁酸对大鼠肝脏过氧化物酶体增殖剂激活受体αmRNA表达的影响[J].河北医科大学学报, 26(5): 368~369.
赵玉琼,要春涛,刘亚千,黄丽洁,赵亚力,赵权,陈华. 2008.我国特有三个小型猪品系PPARα基因的多态性分析[J].中国比较医学杂志, 10(18): 41~44.
Adams M, Reginato M J, Shao D, Lazar M A, Chatterjee V K. 1997.Transcriptional activation by peroxisome proliferator- activated receptor gamma is inhibited by phosphorylation at a consensus mitogen- activated protein kinase site [J]. J Biol Chem, 272: 5128~5132.
Agarwal AK, Garg A. 2002. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familiar partial lipodystrophy [J].Clin Endocrinol Metab, 87: 408~ 411.
Ahluwalia M, Evans M, Morris K, Currie C, Davies S, Rees A, Thomas A. 2002. The influence of the Por12Ala mutation of the PPAR-gamma receptor gene on metabolic and clinical characteristics in treatment-native patients with type2 diabetes [J]. Diabetes Obes Metab, 4 (6): 376~378.
Akiyama TE,Lamhert G, Nicol CJ, Matsusue K, Peters JM, H. Bryan Brewer Jr, and Gonzalez FJ. 2004. Peroxisome proliferators-activated receptor beta/delta regulates very low density lipoprotein production and catabolism in mice on a western diet [J]. Biol Chem, 279: 20874~20881.
Anandharajan R, Pathmanathan K, Shankernarayanan NP, Vishwakarma RA, Balakrishnan A. 2005. Upregulation of Glut-4 and PPAR gamma by an isoflavone from Pterocarpus marsupium on L6 myotubes: a possible mechanism of action [J]. J Ethnopharmacol, 97(2): 253~260.
Andrulionyte L, Kuulasma T, Chiasson JL, Laakso M. 2007. Single nucleotide polymorphisms of the Peroxisome proliferator-activated receptor alpha gene (PPARα) influence the conversion from impairedglucose tolerance to type 2 diabetes: the STOP-NIDDM trial [J].Diabetes, 56(4): 1181~1186.
Arimura N, Horiba T, Imagana M, Shimizu M, and Sato R. 2004. The peroxisome proliferator- activated receptor gamma regulates expression of the perilipin gene in adipocytes [J]. J Biol Chem, 279 (11): 10070~10076.
Balcerzyk A, Zak I, Krauze J. 2007. Synergistic effect between polymorphisms of PPARαand ABCA1 genes on the premature coronary artery disease [J]. Acta Cardiol, 62(3): 233~238.
Barbara PA, Stephen MS, Avery LM, Anca DP, Olga IL, Andrew SG, and Friedhelm S. Sterol carrier Protein-2 expression modulates protein and lipid composition of lipid droplets [J]. J Biol Chem, 2001, 276 (27): 25324~25335.
Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP. 2000. Deactivation of Peroxisome proliferator-activated receptor-αduring cardiac hypertrophic growth [J]. J clin Invest, 105:1723~1730.
Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, Maslen1 GLI, Williams TD M , Lewis H, Schafer AJ , Chatterjee VKK & O'Rahilly S. 1999. Dominant negative mutations in human PPAR gamma associated with severe insulin resistance, diabetes mellitus, and hypertension [J]. Nature, 402: 880~883.
Bastie C, Holst D, Gaillard D, Jehl-Pietri C, Grimaldi PA. 1999. Expression of peroxisome proliferator -activated receptor PPARdelta promotes induction of PPARgamma and adipocyte differentiation in 3T3C2 fibroblasts [J]. J Biol Chem, 274: 21920~21925.
Bastie C, Luquet S, Holst D, Jehl-Pietri C, Grimaldi PA. 2000. Alterations of peroxisome proliferator- activated receptor delta activity affect fatty acid-controlled adipose differentiation [J]. J Biol Chem, 275: 38768~38773.
Berger J, Moler D E. 2002. The mechanisms of action of PPARs [J]. Annu Rev Med, 53: 409~435.
Berger JP, A kiyama TE, Meinke PT. 2005. PPARs: therapeutic targets for metabolic disease [J]. Ternds Phannacol Sci, 26(5):244~251.
Bettina K, Alexander K, Karen G, Batsuch D, Klaus E and Gabriele IS. 2008. Monocarboxylate transporter (MCT)-1 is up-regulated by PPARα[J]. Biochimica et Biophysica Acta, 1780: 899~904.
Braissant O, Foufele F, Scoto C, Dauca M and Wahli W. 1996. Differential expression of peorxisome porliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and-gamma in the adult rat [J] .Endocrinology, 137: 354~366.
Brasaemle DL, Rubin B, Harten IA, Gruia-Gray J, Kimmel AR, Londos C. 2000. Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis [J]. J Biol Chem, 275(49): 38486 ~38493.
Brockman TA, Gupta RA, Dubois RN. 1998. Activation of PPAR gamma leads to inhibition of anchorage independent growth of human colorectal cancer cells [J]. Gastroenterology, 115: 1049~1055.
Brown JD, Plutzkyl. 2007. Peorxisome porliferator-activated receptors as transcriptional nodal Points and therapeutic targets [J]. Circulation, 115(4): 518~533.
Brunmair B, Stamek K, Dorig J, Sz?cs Z, Stadlbauer K, Marian V, Gras F, Anderwald C, Nohl H, Waldh?usl W and Fürnsinn C . 2006. Activation of PPARdelta in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids [J]. Diabetologia, 49: 2713~2722.
Camp HS, Tafuri SR. 1997. Regulation of peroxisome proliferator-activated receptor gamma activity by mitogen-activated protein kinase [J]. J Biol Chem, 272: 10811~10816.
Campbell FM, Kozak R, Wagner A, Altarejos JY, Dyck JR, Belke DD, Severson DL, Kelly DP, Lopaschuk GD. 2002. A role for peroxisome proliferator-activated receptor alpha (PPARalpha) in the control of cardiac malonyl-CoA levels: reduced fatty acid oxidation rates and increased glucose oxidation rates in the hearts of mice lacking PPARalpha are associated with higher concentrations of malonyl-CoA and reduced expression of malonyl-CoA decarboxylase [J]. Biol Chem, 277: 4098~4103.
Castroe-Chavez F , Yechoor VK, Saha PK, Martinez-Botas1 J, Wooten EC , Sharma S, O’Connell P, Taegtmeyer H, and Chan L. 2003. Coordinated up-regulation of oxidative pathways and down-regulation of lipid biosynthesis underlie obesity resistance in perilipin knockout mice: A microarray gene expression profile [J]. Diabetes, 52 (11): 2666~2674.
Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA. 1994. Peroxisome prolifeator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation [J]. Endocrinology, 135(2):798~800.
Chawla A, Lee CH, Barak Y, Weimin H, John R, Debbie L, Jungyeob H, Heonjoong K, and Ronald M E. 2003. PPARδis a very low-density lipoprotein sensor in macrophages [J]. Proc Natl Acad Sci USA, 100: 1268~1273.
Chitturi S, Farrell GC. 2001. Etiopathogesis of nonalcoholia steatohepatitis [J]. Semin Liver Dis, 21(1): 27~41.
Cohen AW, Razani B, Schubert W, Williams TM, Wang XB, Iyengar P, Brasaemle DL, Scherer PE, Lisanti MP. 2004. Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation [J]. Diabetes, 53: 1261~1270.
Corella D, Qi L, Sorli JV, Godoy D, Portoles O, Coltell O, Greenberg AS, MOrdovas J. 2005. Obese subjects carrying the 11482GNA polymorphism at the perilipin locus are resistant to weight loss after dietary energy restriction [J]. J. Clin Endocrinol Metab, 905: 5121~5126.
Corella D, Qi L, Tai ES, Deurenberg-Yap M, Tan CE, Chew SK, Ordovas JM. 2006. Perilipin gene variation determines higher susceptibility to insulin resistance in Asian women when consuming a high- saturated fat, low-carbohydrate diet [J]. Diabetes Care, 29: 1313~1319.
David KK, Lubna A, Swbastio P, Josefin S, Per W, Katja K, Harriet W-H, Ewa E, Juleen RZ, and Anna K. 2005. Direct activation of glucose transport in Primary human myotubes after activation of peroxisome proliferators-activated receptor delta [J]. Diabetes, 54: 1157~1163
Debard C, Cozzone D, Ricard Julien Vouillarmet N, Disse E, Husson B, Laville M and Vidal H. 2006. Short-term activation of peroxisome proliferator-activated receptor beta/delta increases fatty acid oxidation but does not restore insulin action in muscle cells from type 2 diabetic Patients [J].J Mol Med, 84:747~752.
Desvergne B, Michalik L, Wahli W. 2004. Benfit or be sick: peroxisome proleferator- activated receptors are down the road [J]. Mol Endocrinol, 18: 1321.
Diep QN, Touyz RM, Schiffrin EL. 2000. Docosahexaenoic acid, a peroxisome proliferator-activated receptor-alpha ligand, induces apoptosis in vascular smooth muscle cells by stimulation of p38 mitogen- activated protein kinase [J]. Hypertension, 36: 851~855.
Dogan S, Machicao F, Wallwiener D, Haering H, Diedrich K, Hornung D. 2004. Association of perioxisome proliferators-activted receptor gamma 2 Pro-12-Ala polymorphism with endometriosis [J]. Fertility and Sterility, 81(5): 1411~1413.
Doney AS, Fischer B, Cecil JE, Boylan K , McGuigan FE , Ralston SH , Morris AD and Palmer CN .2004. Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to type 2 diabetes [J]. Diabetologia, 47(3): 555~558.
Doney AS, Fischer B, Lee SP, Morris AD, Leese G, Palmer CN. 2005. Association of common variation in the PPARA gene with in individuals with type 2 diabetes: a Go-DARTS study [J]. Nucl Recept, 3:4.
Dreesel U, Alien TL, Pippal JB, Rohde PR, Lau P, and Muscat George EO. 2003. The peroxisome proliferator-activated receptorδ/βagonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells [J]. Mol Endocrine, 17(12): 2477~2493.
Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. 1992. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors [J].Cell, 68: 879~887.
Elizabeth SC, Diego RM, Tatiane KF, Maysa SC, Luiz RR, Lara QA, Rommel RB and Marília de A C S. 2010. Association of PPARαgene polymorphisms and lipid serum levels in a Brazilian elderly population [J]. Experimental and molecular pathology, 88: 197~201.
Evans D, Aberle J, Wendt D, Wolf A, Beisiehel U, and Mann W A. 2001. A polymorphism, L162V, in the peroxisome proliferator–activated receptorα(PPARα) gene is associated with lower body mass index in patients with non-insulin-dependent diabetes mellitus [J]. J Mol Med. 79(4): 198~204.
Evans RM, Barish GD, Wang YX. 2004. PPARs and the complex journey to obesity [J].Nat Med, 10 (4): 355~361.
Everett L, Galli A, Grabb D. 2000. The role of hepatic Peroxisome proliferator-activated receptors (PPARs) in health and disease [J]. Liver, 20: 191~199.
Fajas L, Auboeuf D, Raspe E, Schoonjans K, Lefebvre A-M , Saladin R, Najib J , Laville M, Fruchart J-C, Deeb S, Vidal-Puig A , Flier J , Briggs M R, Staels B, Vidal H and Auwerx J. 1997. The organization, promoter and expression of the human PPAR gamma gene [J].J Biol Chem, 272(30): 18779~18789.
Finck BN, Lehman JJ, Leone CT, Welch MJ, Bennett MJ, Kovacs A, Han X, Richard WG, Kozak R , Lopaschuk GD, and Kelly DP. 2002. The cardiac phenotype induced by PPARαoverexpression mimics that caused by diabetes mellitus [J].J Clin Invest, 109: 12l~130.
Flavell DM, Jamshidi Y, Hawe E. 2002. Peroxisome proliferator-activated receptor alpha gene variants influence Progression of coronary atherosclerosisand risk of coronary artery disease [J]. Circulation, 105(12): 1440~1445.
Forcheron F, Legedz L, Chinetti G, Feugier P, Letexier D, Bricca G, Beylot M. 2005. Genes of cholesterol metabolism in human atheroma: Overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression [J]. Arteroscler Thromb Vasc Biol, 25 (8): 1711~1717.
Gaiping W, Robert R, Klaus E. 2010. Mouse OCTN2 is directly regulated by peroxisome proliferator- activated receptorα(PPARα) via a PPRE located in the first intron [J]. Biochemical Pharmacology, 79: 768~776.
Garcia A, Sekowski A, Subramanian V, Brasaemle DL. 2003. The central domain is required to target and anchor perilipin A to lipid droplets [J]. J Biol Chem, 278(1): 625~635.
Gaudel C, Schwartz C, Giordano C, Abumrad NA, Grimaldi P. 2008. Pharmacological activation of PPAR {beta} promotes rapid and calcineurindependent fiber remodeling and angiogenesis in mouse skeletal muscle [J]. Am. J. Physiol. Endocrinol. Metab, 295: E297~E304.
Gearing KL, Crickmore A, Gustafsson JA. 1994. Structure of the mouse Peroxisome proliferator-activated receptor-alpha gene [J]. Biocbem Biophys Res Commun, 199(1): 255~263.
Grant DB, Vihang AN, Ronald ME. 2006. PPARδ: a dagger in the heart of the metabolic syndrome[J]. The Journal of Clinical Investigation, 116(3): 590~597.
Grarup N, Albrechtsen A , Ek J, J?rgensen T, Schmitz O, Hansen T and Pedersen O. 2007. Variaiton in the peorxisome porliferator-activated receptor delta gene in relation to common metabolic traits in 7,495 middle-aged white people [J]. Diabetologia, 50: 1201~1208.
Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C. 1991. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets [J]. J Biol chem, 266 (17): 11341~11346.
Grimaldi PA. 2003. Roles of PPARδin the control of muscle development and metabolism [J]. Biochem Soc Trans, 31(6): 1130~1132.
Gr(?)nke S, Beller M, Fellert S, Ramakrishnan H, J?ckle H, Kühnlein RP. 2003. Control of fat storage by adrosophila PAT domain Protein [J]. Curr Bio, 13 (7): 603~606.
Guan Y, Breyer MD. 2001. Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease[J]. Kidney Int, 60: 14~30.
Guan YZ, hangY, Breyer MD. 2002. The role of PPARs in the transcriptional control of cellular processes [J]. Drug News and Perspective, 15: 147~154.
Gumel M, Savage DB, Chatterjee VK, O'Rahilly S. 2003. The metabolic syndrome: peroxisome porliferator-activated receptor gamma and its therapeutic modulation [J]. J Clin endocrinol Metab, 88(6): 2412~2421.
Hager J, Dina C, Francke S, Dubois S, Houari M, Vatin V, Vaillant E, Lorentz N, Basdevant A, Clement K, Guy-Grand B, Froguel P. 1998. A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10 [J]. Nat Genet, 20: 304~308.
Hamm JK, Eljack AK, Pilch PF. 1999. Role of PPAR Gamma in Regulating Adipocyte Diferenting and Insulin-responsive Glucose up take [J]. Animals of the New York Academy of Sciences, 892: 134~145.
He W, Barak Y, Hevener A, Olson P, Liao D, Le J, Nelson M, Ong E, Olefsky JM, Evans RM. 2003. Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle [J]. Porc Natl Acad Sci USA, 100(26): 15712~15717.
Hegele RA, Cao H, Frankowski C, Mathews ST, Le VT. 2002. PPARG F338L, a transactivation deficient mutant, in familial partial lipodystrophy [J]. Diabetes, 51: 3586~3590.
Heo M, Leibel RL, Fontaine KR, Boyer BB, Chung WK, Koulu M, Karvonen MK, Pesonen U, Rissanen A, Laakso M , Uusitupa MI, Chagnon Y, Bouchard C, Donohoue PA, Burns TL, Shuldiner AR, Silver K, Andersen RE, Pedersen O, Echwald S, Sorensen TI, Behn P, Permutt MA, Jacobs KB, Elston RC, Hoffman DJ, Gropp E, Allison DB. 2002. A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference [J]. Int J Obes, 26 (5): 640~647.
Hgashiyama H, Bilin AN, OkamotoY, Kinoshita M, Asano S. 2007. Expression profiling of Peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray [J]. Histochemistry and Cell Biology, 127(5): 485~494.
Holst D, Luquet S, Nogueim V, Kristiansen K, Leverve X and Grimaldi PA. 2003. Nutritional regulation and role of peroxisome prolifcrator-activated receptorδin fatty acid catabolism in skeletalmuscle [J]. Bio Chim Biophys Aeta, 1633: 43~50.
Holzapfel J, Heun R, Lütjohann D, Jessen F, Maier W, and K?lsch H. 2006. PPARδhaplotype influences cholesterol metabolism but is no risk factor of Alzheimer’s disease [J]. Neuroscience Letters, 408(1): 57~61.
Hondares E, Pineda-Torra I, Iglesias R, Staels B, Villarroya F, Giralt M. 2007. PPARdelta, but not PPARalPha, activates PGC-l alpha gene transcription in muscle [J].Biochem Biophys Res Commun, 354: 1021~1027.
Hu E, Siegrist-Kaiser CA, Yen PM, Wahli W, Burger AG, Chin WW and Meier C A. 1996.The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin [J]. Endocrinology, 137: 4499~4502.
Hye Won Kang, Keishi Kanno, Erez F. Scapa, David E. Cohen. 2010. Regulatory role for hosphatidy- lcholine transfer protein/StarD2 in the metabolic response to peroxisome proliferator activated receptor alpha (PPARα) [J].Biochimica et Biophysica Acta, 1801: 496~502.
Inquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J, Rassoulzadegan M, and Grimaldi PA. 2003. Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability [J]. FASEBJ, 17: 2299~2301.
Ip E, Farrell GC, Romertson G, Hall P, Kirsch R, Leclercq I. 2003. Central role of PPAR alpha dependent hepatic lipid turnover in dietary steatohepatitis in mice [J]. Hepatology, 38(1): 123~132.
Jean-Charles F. 2009. Peroxisome proliferator-activated receptor-alpha (PPARα): At the crossroads of obesity, diabetes and cardiovascular disease [J]. Atherosclerosis, 205: 1~8.
Josefin Skogsberg. 2003. Evidence that peorxisome porliferator-acitvated receptor delta influences cholesterol metabolism in men [J]. Arterioscler thromb vasc boil, 1:637~643.
Juge-Aubry CE, Hammar E, Siegrist-Kaiser C, Takeshita A, Chin WW, Burger AG, Meier CA, Hammar E. 1999. Regulation of the transcriptional activity of the peroxisome proliferator-activated receptor alpha by phosphorylation of a ligand-independent transactivating domain [J]. J Biol Chem, 274: 10505~10510.
Kang ES, Hur KY, Cha BS, Lee HJ, Kim HJ, Shim WS, Ahn CW, Kim SH, Lee HC. 2006. The 11482GNA polymorphism in the perilipin gene is associated with weight gain with rosiglitazone treatment in type 2 diabetes [J]. Diabetes Care, 29: 1320~1324.
Kanno K, Wu MK, Scapa EF, Roderick SL, Cohen DE. 2007. Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2 [J]. Biochim. Biophys. Acta, 1771: 654~662. Kast-Woelbern HR, Dana SL, Cesario RM, de Grandpre LY, Brooks ME, Osburn DL, Reifel-Miller A,
Klausing K, Leibowitz MD. 2004. Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis [J].Biol Chem, 279(23): 908~915.
Ke Y, Qiu J, Ogus S, Shen WJ, Kraemer FB, Chehab FF. 2003. Overexpression of leptin in transgenic mice leads to decreased basal lipolysis, PKA activity, and perilipin levels [J]. Biochem Biophys Res Commun, 312: 165~1170.
Kern PA, Di Gregorio G, Lu T, Rassouli N, Ranganathan G. 2004. Perilipin expression in human adipose tissue is elevated with obesity [J]. J Clin Endocrinol Metab, 89: l352~1358.
Kim H, Jung T, Kang E, Kim D, Ahn C, Lee K, Lee H, Cha B. 2007. Depot-specific regulation ofperilipin by rosiglitazone in a diabetic animal model [J]. Metabolism, 56 (5): 676~685.
Kim SE, Park JH ,Cho YW, Chung H, Jeong SY, Lee EB and Kwon IC. 2003. Porous chitosan scaffold containing microspheres loaded with transforming growth factor-betal: implications for cartilage tissue engineering [J]. J Control Release, 91(3): 365.
Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM. 2007. A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity [J]. Science, 315: 525~528.
Koh EH, Kim MS, Park JY, Kim HS , Youn JY, Park HS, Youn JH, and Lee KU . 2003. Peroxisome proliferator-activated receptor (PPAR)-alpha activation prevents diabetes in OLETF rats: comparison with PPAR-gamma activation [J]. Diabetes, 52: 2331~ 2337.
Korhonen S, Heinonen S, Hiltunen M , Helisalmi S, Hippel?inen M, Koivunen R, Tapanainen JS andLaakso M. 2003. Polymorphism in the peroxisome proliferators-activated receptor gamma gene in women with polycystic ovary syndrome [J]. Hum Reprod, 18(3): 540~543.
Kota BP, Huang TH, Roufogalis BD. 2005. An overview on biological mechanisms of PPARs [J]. harmacol Res, 51(2): 85~94.
Kuenzli S, Saurat JH. 2003. Peroxisome proliferator-activated receptors in cutaneous biology [J].Br J Dermatol, 149(2): 229~236.
Lacquemoat C, Lepretre F, Pinend Torre I. 2000. Mutation sequencing of the PPARαgene in type2 diabetes association with coronary heart disease [J]. Diabetes & Metabolism, 26(4): 393.
Lapsys NM, Kriketos AD, Lim Fraser M, Poynten AM, Lowy A, Furler SM, Chisholm DJ, and Cooney GJ. 2000. Expression of genes involved in lipid metabolism correlate with peroxisome proliferators activated receptor gamma expression in human skeletal muscle [J].J Clin Endocrinol Metab, 85: 4293 ~ 4297.
Lazar MA. 2005. PPAR gamma, 10 years later [J]. Biochimie, 87 (1): 9~13.
Lazennec G, Canaple L, Saugy D. 2000. Activation of Peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators [J]. Mol Endoccninnol, 14(12): 1962.
Lazennec G, Canaple L, Saugy D, Walter Wahli. 2000. Activation of peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators [J]. Mol Endocrinol, 14: 1962~1975.
Lee CH, Olson P, Hevener A, Isaac M, Chong LW, Olefsky JM, Gonzalez FJ, Ham J, Kang H, Peters JM, and Evans RM. 2006. PPAR delta regulates glucose metabolism and insulin sensitivity [J].Proc Natl Acad sci USA, 103: 3444~3449.
Lee MS, Kliewer SA, Procencal J, Wright PE, Evans RM. 1993. Structure of the retinoid X receptor alpha DNA binding domain: a helix required for homodimeric DNA binding. Science, 260: 1117-1121.
Lee SS, Cgan WY, Lock, Wan DC, Tsang DS, Cheung WT. 2004. Requirement of PPAR alpha in maintaining phospholipids and triacylglycerol homeostasis during energy deprivation [J].J Lipid Res, 45(11): 2025~2037.
Lefebvre P, Chlinetti G, Fruchart JC, and Bart S. 2006. Sorting out the roles of PPARαin energy metabolism and vascular homeostasis [J]. J Clin Invest, 116(3): 571~580.
Londos C, Brasaemle DL, Schultz CJ, Adler-Wailes DC, Levin DM, Kimmel AR, Rondinone CM. 1999. On the control of lipolysis in adipocytes [J]. Ann N Y Acad Sci, 892: 155~168.
Luz Ibarra-Lara , Luz G. Cervantes-Pérez a, Francisca Pérez-Severiano, Leonardo Del Valle, EstherRubio-Ruiz , Elizabeth Soeria-Castro, Gustavo S Pastelin-Hernandez, María Sanchez-Aguilar, Juan C Martrnez-Lazcano, Alicia Sanchez-Mendoza. 2010. PPARαstimulation exerts a blood pressure lowering effect through different mechanisms in a time-dependent manner [J]. European Journal of Pharmacology, 627: 185~193.
Mahoney DJ, Parise G, Melov A, Safdar SA, and Tarnopolsky MA. 2005. Analysis of global mRNA expression in humans keletal muscle during recovery form endurance exercise [J]. FASEBJ, 9: 1498~1500.
Marcinkiewicz A, Gauthier D, Garcia A, Brasaemle DL. 2006. The phosphorylation of serine 492 of perilipin a directs lipid droplet fragmentation and dispersion [J]. J Biol Chem, 281 (17): 11901~11909.
María del Carmen González, J. Christopher Corton, Herrera E, Bocos C. 2009. Peroxisome proliferator-activated receptor-α(PPARα) agonists down-regulatesα2-macroglobulin expression by a PPARα-dependent mechanism [J]. Biochimie, 91: 1029~1035.
Marx N, Duez H, Fruchart JC, Staels B. 2004. Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells [J]. Circ Res, 4(9): 1168~1178.
Michalil L, Desvergne B, Wahli W. 2004. Peroxisome proliferator-activated receptor and cancers: complex stories [J]. Nat Rev Cancer, 4: 61~70.
Michung Yoon. 2009. The role of PPARαin lipid metabolism and obesity: Focusing on the effects of estrogen on PPARαactions [J]. Pharmacological Research, 60: 151~159.
Min-Jeong Shin, Alka M. Kanaya, Ronald M. Krauss. 2008. Polymorphisms in the peroxisome proliferator activated receptorαgene are associated with levels of apolipoprotein CIII and triglyceride in African-Americans but not Caucasians [J]. Atherosclerosis, 198: 313~319.
Miyoshi H, Perfield JW 2nd, Souza SC, Shen WJ, Zhang HH, Stancheva ZS, Kraemer FB, Obin MS, Greenberg AS. 2007. Control of adipose triglyceride lipase action by serine 517 of perilip in A globally regulates protein kinase A-stimulated lipolysis in adipocytes [J]. J Biol Chem, 282 (2): 996~1002.
Mooney RA, Bordwell KL. 1991. Counter-regulation by insulin and isoprenaline of a prominent fat-associated phosphoprotein doublet in rat adipocytes [J]. Biochem J, 274 (Pt2):433~438.
Mori H, Ikegami H , Kawaguchi Y , Seino S , Yokoi N , Takeda J , Inoue I , Seino Y , Yasuda K , Hanafusa T, Yamagata K , Awata T , Kadowaki T , Hara K , Yamada N , Gotoda T, Iwasaki N , Iwamoto Y, Sanke T, Nanjo K, Oka Y, Matsutani A, Maeda E and Kasuga1 M. 2001. The Pro12→Ala substitution in PPARγis associated with resistance to development of diabetes in the general populatins: possible involvement in impairment of insulin secretion in individuals with type2 diabetes [J]. Diabetes, 50(4): 891 ~ 894.
Mossner R, Kaiser R,Matern P, Krüger U, Westphal G, Brockm?ller J, Ziegler A , Neumann C, K?nig IR and Reich K. 2004. Variations in the genes encoding the peroxisome proliferator-activated receptorsαandγin psoriasis [J]. Arch Dermatol Res, 296(1):1~5.
Mottagui-Tabar S, Ryden M, Lofgren P, Faulds G, Hoffstedt J, Brookes AJ, Andersson I, Arner P. 2003. Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis [J]. Diabetologia, 46: 789~797.
Mynatt RL, Stephens JM. 2001.Agouti regulates adipocyte transcription factors[J]. Am J Physiol Cell Phusiol, 2001, 280(4): C 954~961
Nagai S, Shimizu C , Umetsu M, Umetsu M, Taniguchi S, Endo M, Miyoshi H, Yoshioka N, Kubo M, and Koike T. 2004. Identification of a functional peroxisome proliferator-activated receptor responsiveelement within the murine perilinp in gene [J]. Endocrinology, 145 (5): 2346~2356.
Neve BP, Fruchart JC, Staels B. 2000. Role of the peroxisome proliferator-activated receptors (PPARs) in atherosclerosis [J]. Biochemical Pharmacology, 60: 1245~1250.
Nishiu J, Tanaka T, Nakamura T. 1998. Isolation and chromosomal mapping of the human homolog of perilipin (PLIN), a rat adipose tissue-specific gene, by differential display method [J]. Genomcis, 48 (2): 254~257.
Olefsky JM. 2000. Treatment of insulin resistance with peroxisome proliferator- activated receptor- gamma agonist [J]. J Clin Invest, 106(4): 467~472.
Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM. 2001. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport [J].Proc Natl Acad Sci USA, 98: 5306~5311.
Orio Jr F, Matarese G, Biase S Di, Palomba S, Labella D, Sanna V, Savastano S, Zullo F, Colao A and Lombardi G. 2003. Exon6 and 2 peroxisome proliferators- activated receptor gamma polymorphism in polycystic ovary syndrome [J]. J Clin Endocrinol Metab, 88(12): 5887~5892.
Orita M, Suzuki Y, Sekiya T, Hayashi K. 1989. Rapid and sensitive detection of mutations and DNA polymorphisms using the polymerase chain reaction [J]. Genomics, 5: 8741.
Orita M, Suzuki Y, Swkiya T, Hayashi K. 1989. Rapid and sensitive detection of point mutations and genetic polymorphism using polymerase chain reaction [J]. Genomics, 5: 874~879.
Park SY, Pajvani U, McCormack FX, Kim HJ, Higashimori T, Hong EG, Lee MK, Danton C, Deshmukh S, Cline GW, Wu JJ, Bennett AM, Rothermel B, Kalinowski A, Russell KS, Kim YB, Kelly DP, Kim JK. 2005. Cardiac-specific overexpression of peroxisome proliferator-activated receptor-αcauses insulin resistance in heart and 1iver [J]. Diabetes, 54: 2514~2524
Peng DQ, Zhao SP, Nie S, Li J. 2003. Gene-gene interaction of PPARg and ApoE affects coronary heart disease risk [J]. International Journal of Cardiology, 92: 257~263.
Perez-Martinez P, Yiannakouris N, Lopez-Miranda J, Arnett D, Tsai M, Galan E, Straka R, Delgado- Lista J, Province M, Ruano J, Borecki I, Hixson J, Garcia-Bailo B, Perez-Jimenez F, Ordovas JM. 2008. Postprandial triacylglycerol metabolism is modified by the presence of genetic variation at the perilipin (PLIN) locus in 2 white populations [J]. Am J Clin Nutr, 87 (3): 744~752.
Peters JM, Lee SST, Li W, Wen L, Jerrold M. Ward, Gavrilova O, Everett C, Reitman ML, Hudson LD, and Gonzalez FJ. 2000. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptorβ(δ) [J]. Mol Cell Biol, 20(14): 5119~5128.
Peters JM, Yokota T, Vasseur F, Fievet C, Gonzalez FJ. Auwerx J, Hennuyer N. 1997. Altemtions in hpoprotein metabohsm in peroxisome proliferators-activated receptorα-deficient mice [J]. J Biol Chem, 272: 27307~27312.
Picard F, Auwerx J. 2002. PPAR (gamma) and glucose homeostasis [J]. Annu Rev Nutr, 22:167~197.
Pishva H, Mahboob S, Mehdipour P, Eshraghian M, Mohammadi-Asl J, Hosseini S, Rahmany M. 2009. Association between the FABP2 Ala54Thr, PPARa Leu162/Val, and PPARa intron7 polymorphisms and blood lipids ApoB and ApoCIII in hypertriglyceridemic subjects in Tehran [J]. Journal of Clinical Lipidology, 3: 187~194.
Plutzky J. 2003. PPARs as therapeutic targents: reverse cardiology? [J]. Science, 302: 406~407.
Qi L, Corella D, Sorli J V, Portoles O, Shen H, Coltell O, Godoy D, Greenberg AS, J Ordovas M. 2004. Genetic variation at the perilipin (PLIN) locus is associated with obesity-related phenotypes in White women [J]. Clin Genet, 66299~310.
Qi L, Shen H, Larson I, Schaefer EJ, Greenberg AS, Tregouet DA, Corella D, Ordovas JM. 2004. Gender-specific association of a perilipin gene haplotype with obesity risk in a white population [J]. Obes Res, 12: 1758~1765.
Qi L, Tai E S, Tan C E, Shen H, Chew S K, Greenberg A S, Corella D, Ordovas J M. 2005. Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population [J]. J. Mol. Med., 83: 448~456.
Qi L, Zhang CL, Greenberg A, Hu FB. 2008. Common variations in perilipin gene, central obesity, and risk of type 2 diabetes in US women [J]. Obesity, 16: 1061~1065.
Qu S,Su D,Altomonte J, Kamagate A, He J, Perdomo G, Tse T, Jiang Y, and Dong HH. 2007.PPAR｛alpha｝mediates the hypolipidemic action of fibrates by antagonizing FoxO1 [J]. American Journal of Physiology-Endocrinology and Metabolism, 292(2): E421~434.
Rangwala SM, hazar MA. 2004. Peroxisome proliferator-activated receptor gamma in diabetes and metabolism [J]. Trends Pharmacol Sci, 25(6):331~336.
Reddy. 2001. Nonalcoholic steatosis and steatohepatitisⅢperoxisomal beta-oxidation, PPAR alpha, and steatohepatitis [J].Am J Physiol Gastrointest Liver Physiol, 281(6): G1333~G1339.
Ren XD, Lu YQ, Ye KH. 2005. The antitumor molecular machnisms of non steroid anti-inflammatory drugs [J]. Chin Pharmacol Bull, 21: 527~531.
Ricote M, Glass CK. 2001. New roles for PPARs in cholesterol homeostasis [J].Trends Pharmacol Sci, 22(9): 441~443: discussion 444.
Rieck M, Wedeken L, Muller-Brusselbach S, Meissner W and Müller R. 2007. Expression level and agonist-binding affect the turnover, ubiquitination and complex formation of peroxisome proliferator- activated receptor-β[J]. FEBSJ, 274: 5068~5076.
Ristow M, Muller-Wieland D, Pfeiffer A, Krone W, Kahn CR.1998. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation [J]. N Engl J Med, 339 (14): 953 - 959.
Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM. 2002. C/EBP- alpha induces adipogenesis through PPARgamma: a unified pathway [J]. Genes Dev, 16(1): 22~26.
Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. 1999. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro [J].Mol Cell, 4 (4): 611~617.
Rotimi CN, Comuzzie AG, Lowe WL, Luke A, Blangero J, Cooper RS. 1999. The quantitative trait locus on chromosome 2 for serum leptin levels is confirmed in African-Americans [J]. Diabetes, 48: 643~644.
Samir Ben Ali , Fatma Ben Yahia , Yousra Sediri, Amani Kallel , Bochra Ftouhi ,Moncef Feki, Monia Elasmi , Sameh Haj-Taieb , Omar Souheil , Haifa Sanhagi,Hedia Slimane b, Riadh Jemaa , Naziha Kaabachi. 2009. Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptorγ-2 gene on obesity risk and leptin levels in a Tunisian population [J]. Clinical Biochemistry, 42: 1642~1647.
Savage DB, Tan GD, Acerini CL, Jebb SA , Agostini M, Gurnell M , Williams RL , Umpleby AM,Louise Thomas E, Bell JD , Dixon AK , Dunne F , Boiani R , Cinti S , Vidal-Puig A , Karpe F, Krishna V, Chatterjee K and O’Rahilly S. 2003. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma [J]. Diabetes, 52: 910~ 917.
Scapa EF, Pocai A, Wu MK, Gutierrez-Juarez R, Glenz L, Kanno K, Li H, Biddinger S, Jelicks LA, Rossetti L, Cohen DE. 2008. Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2 [J]. FASEB J. 22: 2579~2590.
Schmidt A, Endo N, RutledgeS J, Vogel R, Shinar D, Rodan GA. 1992. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids [J]. Mol Endocrinol, 6: 1634~1641.
Seo YS, Kim JH, Jo NY, Choi KM, Baik SH, Park JJ, Kim JS, Byun KS, Bak YT, Lee CH, Kim A, Yeon JE. 2008. PPARagonists treatment is effective in a nonalcoholic fatty liver diseasr animal model by modulating fatty-acid metabolic enztmes [J]. J Gastrenterol Hepatol, 23(1): 102~109.
Shaw N, Elholm M, Noy N. 2003. Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptorβ/δ[J]. J Biol Chem, 278: 41589~41592.
Shin HD, Park BL, Kim LH, Cottel D, Lebel P, Dallongeville J, Deeb S, Auwerx J and Amouyel P. 2004. Genetic polymorphisms in peroxisome proliferator-activated receptorδassociate with obesity [J]. Diabetes, 53: 847~851.
Skogsberg J, McMahon A D, Karpe F, Hamsten A, Packard C J & Ehrenborg E. 2003. Peroxisome proliferators activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men [J]. J Intern Med, 254: 597~604
Soenen S, Mariman EC, Vogels N, Bouwman FG, den Hoed M, Brown L, Westerterp-Plantenga MS. 2009. Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance [J]. Physiology & Behavior, 96: 723~728.
Souza SC, de Vargas LM, Yamamoto MT, Lien P, Franciosa MD, Moss LG, Greenberg AS. 1998. Overexpression of perilipin A and B blocks the ability of tumor necrosis factor alpha to increase lipolysis in 3T3-L1 adipocyte [J]. J Biol Chem, 273(38): 24665~4669
Subramanian V, Garcia A, Sekowski A, Brasaemle D L. 2004. Hydrophobic sequences target and anchor perilipin A to lipid droplets [J]. J Lipid Res, 45 (11): 1983~1991.
Sundvold H, Brzozowska A, and Lien S. 1997. Characterization of bovine peroxisome proliferator- activated receptors gamma 1 and gamma 2: genetic mapping and differential expression of the two isoforms [J]. Biochem. Biophys. Res. Commun. 239 (3): 857~861.
Sztalryd C, Xu G, Doward H, Tansey JT, Contreras JA, Kimmel AR, and Londos C. 2003. Perilipin A is essential for the translocation of Hormone-sensitive lipase during lipolytic activation [J]. J. Cell Biol, 161(6): 1011~1012.
Tahara T, Arisawa T, Shibata T, Nakamura M, Wang F, Maruyama N, Kamiya Y, Nakamura M, Fujita H, Nagasaka M, Iwata M, Takahama K, Watanabe M, Hirata I, Nakano H Nakamura M, Wang F, Maruyama N, Kamiya Y, Nakamura M, Fujita H, Nagasaka M, Iwata M, Takahama K, Watanabe M, Hirata I, Nakano H. 2008. Influence of Peroxisome Proliferator-activated Receptor (PPAR) gamma Plo12Ala Polymorphism as a Shared Risk Marker for Both Gastric Cancer and Impaired Fasting Glucose (IFG) in Japanese [J]. Dig Dis Sci, 53 (3): 614-621.
Tai ES, Demissie S, Cupples LA, corella D, Wilson PW, Schaefer EJ and Ordovas JM. 2002. Association between the PPARαL162V polymorphism and plasma lipid levels: The Framingham Offspring Study [J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 22(5): 805~811.
Takao K, Jing C, and Keith RM. 2001. Magnetic Bead-Isolated Single-Strand DNA for SSCP Analysis. In: Walker, John M. Methods in Molecular Biology [J]. Humana Press, 135~147.
Tanaka T, Yamamoto J, Iwasaki S, Asaba H, Hamura H, Ikeda Y, Watanabe M, Magoori K, Ioka RX, Tachibana K, Watanabe Y, Uchiyama Y, Sumi K, Iguchi H, Ito S, Doi T, Hamakubo T, Naito M, Auwerx J, Yanagisawa M, Kodama T, and Sakai J. 2003. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic Syndrome [J]. Proc Natl Acad sci USA, 100: 15924~15929.
Tanrori Y, Masugi J, Nishino N, Kasuga M. 2002. Role of peroxisome porliferator-activated receptor- gamma in maintenance of the characteristics of mature 3T3-L1 adipocytes [J]. Diabetes, 51(7): 2045~2055.
Tansey JT, Huml AM, Vogt R, Davis KE, Jones JM, Fraser KA, Brasaemle DL, Kimmel AR, and Londos C. 2003. Functional studies on native and mutated forms of perilipin. A role in protein kinase A-mediated lipolysis of triacylglycerols in Chinese hamster ovary cells [J]. J Biol Chem, 278(10): 8401~ 8406.
Tansey JT, Sztalryd C, Gruia-Gray J, Roush DL, Zee JV, Gavrilova O, Reitman ML, Deng CX, Li C, Kimmel AR, Londos C. 2001. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production , and resistance to diet-induced obesity [J]. J PNAS, 98 (11): 6494~6499.
Thomas Lunda?sen, Mary C. Hunt, Lisa-Mari Nilsson Sabyasachi Sanyal, Bo Angelin, Stefan EH. Alexsonc and Mats Rudling. 2007. PPARa is a key regulator of hepatic FGF21 [J]. Biochemical and Biophysical Research Communications, 360: 437~440.
Tontonoz P, Hu E, Spiegelman B M. 1994. Stimulation of adipogenesis in fibroblasts by PPAR gamma2, a lipid-activated transcription factor [J]. Cell, 79 (7): 1147~1156.
Tontonoz P, Hu E, Spiegelman B. 1995. M. Regulation of adipocyte gene expression and differentiation peroxisome porliferator activated receptor gamma [J]. Curr Opin Genet Dev, 5 (5):571~576.
Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM. 1998. PPARgamma promotes monocyte /macrophage differentiation and uptake of oxidized LDL [J]. Cell, 93(2): 241~252.
Tontonoz P, Singer S, Forman B M, Sarraf P, Fletcher JA, Fletcher CD, Brun RP, Mueller E, Altiok S, Oppenheim H, Evans RM, Spiegelman BM. 1997. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferators-activated receptorγand the retinoid X receptor [J]. Proc Natl Acad Sci USA, 94: 237~241.
Toshihide Kawai, Maggie C.Y. Ng a, M. Geoffrey Hayes, Issei Yoshiuchi, Takafumi Tsuchiya, Heather Robertson, Nancy J. Cox , Kenneth S. Polonsky,Graeme I. Bell, David A. Ehrmann. 2009. Variation in the perilipin gene (PLIN) affects glucose and lipid metabolism in non-Hispanic white women with and without polycystic ovary syndrome [J]. Diabetes research and clinical practice, 186~192.
Tsunoda M, Kobayashi N, Ide T, Utsumi M, Nagasawa M, Murakami K.2008. A novel PPAR agonist ameliorates insulin resistance in dogs fed a high-fat diet [J]. Am J Physiol Endocrinol Metab, 294: E833-E840.
Uppenberg J, Svensson C, Jaki M, Bertilsson G, Jendeberg L, Berkenstam A. 1998. Crystal structureof the ligand binding domain of the human nuclear receptor PPARgamma. J Biol Chem, 273(47): 31108 ~31112.
Vanden Heuvel JP. 2007. The PPAR resource page [J].Bio Chim Biophys Acts, 1771(8): 1108 ~1112.
Vantitnen M, Nuutifa P, Kuulasmaa T, Pihlajam?ki J, H?llsten K, Virtanen K A, Lautam?ki R, Peltoniemi P, Takala T, Antti P.M. Viljanen, Knuuti J and Markku Laakso. 2005. Single nucleotide polymorphisms in the peorxisome proliferator-acitvated receptorδgene are associated with skeletal muscle glucose uptake [J].Diabetes, 54: 3587~3591.
Vohl MC, Lepage P, Gaudet D. 2000. Molecular-scanning of the human PPARαgene: association of the L162V mutation with hyperapobtali protein in emia [J]. J Lipid Res, 41(6):945~952.
Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. 2003. Peroxisome proliferator-activated receptor delta activates fat etabolism to prevent obesity [J]. Cell, 113: 159~170.
Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, Bayuga-Ocampo CR , Ham J , Kang H, Evans R M . 2004. Regulation of muscle fiber type and running endurance by PPAR delta [J]. P1oS Biol, 2(10): e294.
Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM. 1999. Cross-regulation of C /EBP Alpha and PPAR Gamma Controls the Transcrip tional Pathway of Adipogenesis and Insulin Sensitivity [J]. Journal of Molecular and Cellular Cardiology, 3: 151 ~158.
Yamada Y, Ando F, Shimokata H. 2006. Association of polymorphisms in forkhead box C2 and perilipin genes with bone mineral density in community-dwelling Japanese individuals [J]. Int. J. Mol. Med, 18: 119~127.
Yamakawa-Kobayashi K, Ishiguro H, Arinami T, Miyazaki R, Hamaguchi H. 2002. A Val 227 Ala polymorphism in the peroxisome proliferator activated receptor alpha (PPAR alpha) gene is associated with variations in serum lipid levels [J]. Jed Genet, 39: 189~191.
Yang LL, Hua Q, Liu RK, and Yang Z. 2009. Association between two common polymorphisms of PPARγgene and metabolic syndrome families in a Chinese population [J]. Archives of Medical Research, 40: 89~96.
Ye P, Wang Z, Zhang XJ, Zhao YL. 2005. Age related decrease in expression of peroxisome proliferators activated receptorαand its effects on development of dyslipidemia [J]. Chin Med J (Engl), 118 (13): 1093~1098.
Yen CJ, Beamer BA, Negri C, Silverb K, Brownb KA, Yarnallc DP, Burnsc DK, Rotha J and Shuldinerb AR. 1977. Molecular scanning of the human peroxisome proliferators activated receptorγ(PPARγ) gene in diabetic Caucasians: identification of a Pro12Ala PPARγ2 missense mutation [J].Biochem Biophy Res Commun, 241: 270~274
Yiannakouris N, Yannakoulia M, Melistas L, Chan JL, Klimis-Zacas D and Mantzoros CS. 2001.The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of bodyweight and body composition variability [J]. J Clin Endocrinol Metab, 86(9): 4434~4439.
Yue Ji-Rong, Dong Bi-Rong, Huang Chang-Quan, Lu Zhen-Chan, Wu Hong-Mei, Zhang Yan-Ling, and Tod A. Mattis. 2009. Pro12Ala Polymorphism in PPARγ2 Associated with Depression in Chinese Nonagenarians/Centenarians [J].Archives of Medical Research, 40: 411~415.
Zhang B, Berger J, Zhou G, Elbrecht A, Biswas S, White-Carrington S, Szalkowski D, and Moller DE.1996. Insulin and mitogen activated protein kinase-mediated phosphorylation and activation of peroxisome proliferator-activated receptor gamma [J]. J Biol Chem, 271: 31771~31774.
Zhang HF, He YX, Chung PK, Tong TK, Fu FH, Chen YJ, Jiao GF. 2009. Effects of 12 weeks of exercise on hepatic TNF-αand PPARαin an animal model of high-fat diet-induced nonalcoholic steatohepatitis [J]. J Exerc Sci Fit, 7 (1): 18~23.
陈雪香,刘合焜. 2008. PPARα基因多态性与2型糖尿病关系研究[J].医学综述, 14(6): 897~899.
邓其兰,余冰,陈代文. 2009.围脂滴蛋白(Perlipin)在脂质代谢中的功能[J].饲料工业, 30(5): 8~9.
胡承,贾伟平,方启晨,张蓉,王从容,陆俊茜,项坤三. 2005. PPARδ87T→C基因多态性与代谢综合征的关联研究[J].中华内分泌代谢杂志, 21: 380~383.
孔保华,陶菲,刁新平. 2002.中国肉牛产业的现状和发展趋势[J].肉类研究, 1: 10~13.
孔路军,王爱国,傅金恋,张毅良,王晓凤. 2006.猪PPARs基因组织表达特性的研究[J].遗传育种, 42(19):1~4
李昕. 2006. PPARγ及apM1基因多态性与多囊卵巢综合征肥胖异质性的相关研究[博士学位论文].上海:复旦大学.
罗锦标,田勇,陶争荣,袁青,李国勤,王德前,原爱平,邹丽丽,卢立志,沈军达,石放雄. 2008. PPAR基因在鹅肥肝形成中的可调节性表达[J].中国农业科学, 41(10): 3270~3276.
孟和,李辉,王宇祥. 2004.鸡PPARs基因组织表达特性的研究[J].遗传学报, 31(7): 682~687.
戚晓红,张昭萍,李晓宇,阕玲俐,吴翠贞. 2003.过氧化物酶体增殖物激活受体在实验性大鼠脂肪肝中的表达[J].中国病理生理杂志, 19(9) : 1206~1209.
石如玲,姜玲玲. 2005.胆汁酸对大鼠肝脏过氧化物酶体增殖剂激活受体αmRNA表达的影响[J].河北医科大学学报, 26(5): 368~369.
赵玉琼,要春涛,刘亚千,黄丽洁,赵亚力,赵权,陈华. 2008.我国特有三个小型猪品系PPARα基因的多态性分析[J].中国比较医学杂志, 10(18): 41~44.
Adams M, Reginato M J, Shao D, Lazar M A, Chatterjee V K. 1997.Transcriptional activation by peroxisome proliferator- activated receptor gamma is inhibited by phosphorylation at a consensus mitogen- activated protein kinase site [J]. J Biol Chem, 272: 5128~5132.
Agarwal AK, Garg A. 2002. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familiar partial lipodystrophy [J].Clin Endocrinol Metab, 87: 408~ 411.
Ahluwalia M, Evans M, Morris K, Currie C, Davies S, Rees A, Thomas A. 2002. The influence of the Por12Ala mutation of the PPAR-gamma receptor gene on metabolic and clinical characteristics in treatment-native patients with type2 diabetes [J]. Diabetes Obes Metab, 4 (6): 376~378.
Akiyama TE,Lamhert G, Nicol CJ, Matsusue K, Peters JM, H. Bryan Brewer Jr, and Gonzalez FJ. 2004. Peroxisome proliferators-activated receptor beta/delta regulates very low density lipoprotein production and catabolism in mice on a western diet [J]. Biol Chem, 279: 20874~20881.
Anandharajan R, Pathmanathan K, Shankernarayanan NP, Vishwakarma RA, Balakrishnan A. 2005. Upregulation of Glut-4 and PPAR gamma by an isoflavone from Pterocarpus marsupium on L6 myotubes: a possible mechanism of action [J]. J Ethnopharmacol, 97(2): 253~260.
Andrulionyte L, Kuulasma T, Chiasson JL, Laakso M. 2007. Single nucleotide polymorphisms of the Peroxisome proliferator-activated receptor alpha gene (PPARα) influence the conversion from impairedglucose tolerance to type 2 diabetes: the STOP-NIDDM trial [J].Diabetes, 56(4): 1181~1186.
Arimura N, Horiba T, Imagana M, Shimizu M, and Sato R. 2004. The peroxisome proliferator- activated receptor gamma regulates expression of the perilipin gene in adipocytes [J]. J Biol Chem, 279 (11): 10070~10076.
Balcerzyk A, Zak I, Krauze J. 2007. Synergistic effect between polymorphisms of PPARαand ABCA1 genes on the premature coronary artery disease [J]. Acta Cardiol, 62(3): 233~238.
Barbara PA, Stephen MS, Avery LM, Anca DP, Olga IL, Andrew SG, and Friedhelm S. Sterol carrier Protein-2 expression modulates protein and lipid composition of lipid droplets [J]. J Biol Chem, 2001, 276 (27): 25324~25335.
Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP. 2000. Deactivation of Peroxisome proliferator-activated receptor-αduring cardiac hypertrophic growth [J]. J clin Invest, 105:1723~1730.
Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, Maslen1 GLI, Williams TD M , Lewis H, Schafer AJ , Chatterjee VKK & O'Rahilly S. 1999. Dominant negative mutations in human PPAR gamma associated with severe insulin resistance, diabetes mellitus, and hypertension [J]. Nature, 402: 880~883.
Bastie C, Holst D, Gaillard D, Jehl-Pietri C, Grimaldi PA. 1999. Expression of peroxisome proliferator -activated receptor PPARdelta promotes induction of PPARgamma and adipocyte differentiation in 3T3C2 fibroblasts [J]. J Biol Chem, 274: 21920~21925.
Bastie C, Luquet S, Holst D, Jehl-Pietri C, Grimaldi PA. 2000. Alterations of peroxisome proliferator- activated receptor delta activity affect fatty acid-controlled adipose differentiation [J]. J Biol Chem, 275: 38768~38773.
Berger J, Moler D E. 2002. The mechanisms of action of PPARs [J]. Annu Rev Med, 53: 409~435.
Berger JP, A kiyama TE, Meinke PT. 2005. PPARs: therapeutic targets for metabolic disease [J]. Ternds Phannacol Sci, 26(5):244~251.
Bettina K, Alexander K, Karen G, Batsuch D, Klaus E and Gabriele IS. 2008. Monocarboxylate transporter (MCT)-1 is up-regulated by PPARα[J]. Biochimica et Biophysica Acta, 1780: 899~904.
Braissant O, Foufele F, Scoto C, Dauca M and Wahli W. 1996. Differential expression of peorxisome porliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and-gamma in the adult rat [J] .Endocrinology, 137: 354~366.
Brasaemle DL, Rubin B, Harten IA, Gruia-Gray J, Kimmel AR, Londos C. 2000. Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis [J]. J Biol Chem, 275(49): 38486 ~38493.
Brockman TA, Gupta RA, Dubois RN. 1998. Activation of PPAR gamma leads to inhibition of anchorage independent growth of human colorectal cancer cells [J]. Gastroenterology, 115: 1049~1055.
Brown JD, Plutzkyl. 2007. Peorxisome porliferator-activated receptors as transcriptional nodal Points and therapeutic targets [J]. Circulation, 115(4): 518~533.
Brunmair B, Stamek K, Dorig J, Sz?cs Z, Stadlbauer K, Marian V, Gras F, Anderwald C, Nohl H, Waldh?usl W and Fürnsinn C . 2006. Activation of PPARdelta in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids [J]. Diabetologia, 49: 2713~2722.
Camp HS, Tafuri SR. 1997. Regulation of peroxisome proliferator-activated receptor gamma activity by mitogen-activated protein kinase [J]. J Biol Chem, 272: 10811~10816.
Campbell FM, Kozak R, Wagner A, Altarejos JY, Dyck JR, Belke DD, Severson DL, Kelly DP, Lopaschuk GD. 2002. A role for peroxisome proliferator-activated receptor alpha (PPARalpha) in the control of cardiac malonyl-CoA levels: reduced fatty acid oxidation rates and increased glucose oxidation rates in the hearts of mice lacking PPARalpha are associated with higher concentrations of malonyl-CoA and reduced expression of malonyl-CoA decarboxylase [J]. Biol Chem, 277: 4098~4103.
Castroe-Chavez F , Yechoor VK, Saha PK, Martinez-Botas1 J, Wooten EC , Sharma S, O’Connell P, Taegtmeyer H, and Chan L. 2003. Coordinated up-regulation of oxidative pathways and down-regulation of lipid biosynthesis underlie obesity resistance in perilipin knockout mice: A microarray gene expression profile [J]. Diabetes, 52 (11): 2666~2674.
Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA. 1994. Peroxisome prolifeator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation [J]. Endocrinology, 135(2):798~800.
Chawla A, Lee CH, Barak Y, Weimin H, John R, Debbie L, Jungyeob H, Heonjoong K, and Ronald M E. 2003. PPARδis a very low-density lipoprotein sensor in macrophages [J]. Proc Natl Acad Sci USA, 100: 1268~1273.
Chitturi S, Farrell GC. 2001. Etiopathogesis of nonalcoholia steatohepatitis [J]. Semin Liver Dis, 21(1): 27~41.
Cohen AW, Razani B, Schubert W, Williams TM, Wang XB, Iyengar P, Brasaemle DL, Scherer PE, Lisanti MP. 2004. Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation [J]. Diabetes, 53: 1261~1270.
Corella D, Qi L, Sorli JV, Godoy D, Portoles O, Coltell O, Greenberg AS, MOrdovas J. 2005. Obese subjects carrying the 11482GNA polymorphism at the perilipin locus are resistant to weight loss after dietary energy restriction [J]. J. Clin Endocrinol Metab, 905: 5121~5126.
Corella D, Qi L, Tai ES, Deurenberg-Yap M, Tan CE, Chew SK, Ordovas JM. 2006. Perilipin gene variation determines higher susceptibility to insulin resistance in Asian women when consuming a high- saturated fat, low-carbohydrate diet [J]. Diabetes Care, 29: 1313~1319.
David KK, Lubna A, Swbastio P, Josefin S, Per W, Katja K, Harriet W-H, Ewa E, Juleen RZ, and Anna K. 2005. Direct activation of glucose transport in Primary human myotubes after activation of peroxisome proliferators-activated receptor delta [J]. Diabetes, 54: 1157~1163
Debard C, Cozzone D, Ricard Julien Vouillarmet N, Disse E, Husson B, Laville M and Vidal H. 2006. Short-term activation of peroxisome proliferator-activated receptor beta/delta increases fatty acid oxidation but does not restore insulin action in muscle cells from type 2 diabetic Patients [J].J Mol Med, 84:747~752.
Desvergne B, Michalik L, Wahli W. 2004. Benfit or be sick: peroxisome proleferator- activated receptors are down the road [J]. Mol Endocrinol, 18: 1321.
Diep QN, Touyz RM, Schiffrin EL. 2000. Docosahexaenoic acid, a peroxisome proliferator-activated receptor-alpha ligand, induces apoptosis in vascular smooth muscle cells by stimulation of p38 mitogen- activated protein kinase [J]. Hypertension, 36: 851~855.
Dogan S, Machicao F, Wallwiener D, Haering H, Diedrich K, Hornung D. 2004. Association of perioxisome proliferators-activted receptor gamma 2 Pro-12-Ala polymorphism with endometriosis [J]. Fertility and Sterility, 81(5): 1411~1413.
Doney AS, Fischer B, Cecil JE, Boylan K , McGuigan FE , Ralston SH , Morris AD and Palmer CN .2004. Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to type 2 diabetes [J]. Diabetologia, 47(3): 555~558.
Doney AS, Fischer B, Lee SP, Morris AD, Leese G, Palmer CN. 2005. Association of common variation in the PPARA gene with in individuals with type 2 diabetes: a Go-DARTS study [J]. Nucl Recept, 3:4.
Dreesel U, Alien TL, Pippal JB, Rohde PR, Lau P, and Muscat George EO. 2003. The peroxisome proliferator-activated receptorδ/βagonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells [J]. Mol Endocrine, 17(12): 2477~2493.
Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. 1992. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors [J].Cell, 68: 879~887.
Elizabeth SC, Diego RM, Tatiane KF, Maysa SC, Luiz RR, Lara QA, Rommel RB and Marília de A C S. 2010. Association of PPARαgene polymorphisms and lipid serum levels in a Brazilian elderly population [J]. Experimental and molecular pathology, 88: 197~201.
Evans D, Aberle J, Wendt D, Wolf A, Beisiehel U, and Mann W A. 2001. A polymorphism, L162V, in the peroxisome proliferator–activated receptorα(PPARα) gene is associated with lower body mass index in patients with non-insulin-dependent diabetes mellitus [J]. J Mol Med. 79(4): 198~204.
Evans RM, Barish GD, Wang YX. 2004. PPARs and the complex journey to obesity [J].Nat Med, 10 (4): 355~361.
Everett L, Galli A, Grabb D. 2000. The role of hepatic Peroxisome proliferator-activated receptors (PPARs) in health and disease [J]. Liver, 20: 191~199.
Fajas L, Auboeuf D, Raspe E, Schoonjans K, Lefebvre A-M , Saladin R, Najib J , Laville M, Fruchart J-C, Deeb S, Vidal-Puig A , Flier J , Briggs M R, Staels B, Vidal H and Auwerx J. 1997. The organization, promoter and expression of the human PPAR gamma gene [J].J Biol Chem, 272(30): 18779~18789.
Finck BN, Lehman JJ, Leone CT, Welch MJ, Bennett MJ, Kovacs A, Han X, Richard WG, Kozak R , Lopaschuk GD, and Kelly DP. 2002. The cardiac phenotype induced by PPARαoverexpression mimics that caused by diabetes mellitus [J].J Clin Invest, 109: 12l~130.
Flavell DM, Jamshidi Y, Hawe E. 2002. Peroxisome proliferator-activated receptor alpha gene variants influence Progression of coronary atherosclerosisand risk of coronary artery disease [J]. Circulation, 105(12): 1440~1445.
Forcheron F, Legedz L, Chinetti G, Feugier P, Letexier D, Bricca G, Beylot M. 2005. Genes of cholesterol metabolism in human atheroma: Overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression [J]. Arteroscler Thromb Vasc Biol, 25 (8): 1711~1717.
Gaiping W, Robert R, Klaus E. 2010. Mouse OCTN2 is directly regulated by peroxisome proliferator- activated receptorα(PPARα) via a PPRE located in the first intron [J]. Biochemical Pharmacology, 79: 768~776.
Garcia A, Sekowski A, Subramanian V, Brasaemle DL. 2003. The central domain is required to target and anchor perilipin A to lipid droplets [J]. J Biol Chem, 278(1): 625~635.
Gaudel C, Schwartz C, Giordano C, Abumrad NA, Grimaldi P. 2008. Pharmacological activation of PPAR {beta} promotes rapid and calcineurindependent fiber remodeling and angiogenesis in mouse skeletal muscle [J]. Am. J. Physiol. Endocrinol. Metab, 295: E297~E304.
Gearing KL, Crickmore A, Gustafsson JA. 1994. Structure of the mouse Peroxisome proliferator-activated receptor-alpha gene [J]. Biocbem Biophys Res Commun, 199(1): 255~263.
Grant DB, Vihang AN, Ronald ME. 2006. PPARδ: a dagger in the heart of the metabolic syndrome[J]. The Journal of Clinical Investigation, 116(3): 590~597.
Grarup N, Albrechtsen A , Ek J, J?rgensen T, Schmitz O, Hansen T and Pedersen O. 2007. Variaiton in the peorxisome porliferator-activated receptor delta gene in relation to common metabolic traits in 7,495 middle-aged white people [J]. Diabetologia, 50: 1201~1208.
Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C. 1991. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets [J]. J Biol chem, 266 (17): 11341~11346.
Grimaldi PA. 2003. Roles of PPARδin the control of muscle development and metabolism [J]. Biochem Soc Trans, 31(6): 1130~1132.
Gr(?)nke S, Beller M, Fellert S, Ramakrishnan H, J?ckle H, Kühnlein RP. 2003. Control of fat storage by adrosophila PAT domain Protein [J]. Curr Bio, 13 (7): 603~606.
Guan Y, Breyer MD. 2001. Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease[J]. Kidney Int, 60: 14~30.
Guan YZ, hangY, Breyer MD. 2002. The role of PPARs in the transcriptional control of cellular processes [J]. Drug News and Perspective, 15: 147~154.
Gumel M, Savage DB, Chatterjee VK, O'Rahilly S. 2003. The metabolic syndrome: peroxisome porliferator-activated receptor gamma and its therapeutic modulation [J]. J Clin endocrinol Metab, 88(6): 2412~2421.
Hager J, Dina C, Francke S, Dubois S, Houari M, Vatin V, Vaillant E, Lorentz N, Basdevant A, Clement K, Guy-Grand B, Froguel P. 1998. A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10 [J]. Nat Genet, 20: 304~308.
Hamm JK, Eljack AK, Pilch PF. 1999. Role of PPAR Gamma in Regulating Adipocyte Diferenting and Insulin-responsive Glucose up take [J]. Animals of the New York Academy of Sciences, 892: 134~145.
He W, Barak Y, Hevener A, Olson P, Liao D, Le J, Nelson M, Ong E, Olefsky JM, Evans RM. 2003. Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle [J]. Porc Natl Acad Sci USA, 100(26): 15712~15717.
Hegele RA, Cao H, Frankowski C, Mathews ST, Le VT. 2002. PPARG F338L, a transactivation deficient mutant, in familial partial lipodystrophy [J]. Diabetes, 51: 3586~3590.
Heo M, Leibel RL, Fontaine KR, Boyer BB, Chung WK, Koulu M, Karvonen MK, Pesonen U, Rissanen A, Laakso M , Uusitupa MI, Chagnon Y, Bouchard C, Donohoue PA, Burns TL, Shuldiner AR, Silver K, Andersen RE, Pedersen O, Echwald S, Sorensen TI, Behn P, Permutt MA, Jacobs KB, Elston RC, Hoffman DJ, Gropp E, Allison DB. 2002. A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference [J]. Int J Obes, 26 (5): 640~647.
Hgashiyama H, Bilin AN, OkamotoY, Kinoshita M, Asano S. 2007. Expression profiling of Peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray [J]. Histochemistry and Cell Biology, 127(5): 485~494.
Holst D, Luquet S, Nogueim V, Kristiansen K, Leverve X and Grimaldi PA. 2003. Nutritional regulation and role of peroxisome prolifcrator-activated receptorδin fatty acid catabolism in skeletalmuscle [J]. Bio Chim Biophys Aeta, 1633: 43~50.
Holzapfel J, Heun R, Lütjohann D, Jessen F, Maier W, and K?lsch H. 2006. PPARδhaplotype influences cholesterol metabolism but is no risk factor of Alzheimer’s disease [J]. Neuroscience Letters, 408(1): 57~61.
Hondares E, Pineda-Torra I, Iglesias R, Staels B, Villarroya F, Giralt M. 2007. PPARdelta, but not PPARalPha, activates PGC-l alpha gene transcription in muscle [J].Biochem Biophys Res Commun, 354: 1021~1027.
Hu E, Siegrist-Kaiser CA, Yen PM, Wahli W, Burger AG, Chin WW and Meier C A. 1996.The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin [J]. Endocrinology, 137: 4499~4502.
Hye Won Kang, Keishi Kanno, Erez F. Scapa, David E. Cohen. 2010. Regulatory role for hosphatidy- lcholine transfer protein/StarD2 in the metabolic response to peroxisome proliferator activated receptor alpha (PPARα) [J].Biochimica et Biophysica Acta, 1801: 496~502.
Inquet S, Lopez-Soriano J, Holst D, Fredenrich A, Melki J, Rassoulzadegan M, and Grimaldi PA. 2003. Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability [J]. FASEBJ, 17: 2299~2301.
Ip E, Farrell GC, Romertson G, Hall P, Kirsch R, Leclercq I. 2003. Central role of PPAR alpha dependent hepatic lipid turnover in dietary steatohepatitis in mice [J]. Hepatology, 38(1): 123~132.
Jean-Charles F. 2009. Peroxisome proliferator-activated receptor-alpha (PPARα): At the crossroads of obesity, diabetes and cardiovascular disease [J]. Atherosclerosis, 205: 1~8.
Josefin Skogsberg. 2003. Evidence that peorxisome porliferator-acitvated receptor delta influences cholesterol metabolism in men [J]. Arterioscler thromb vasc boil, 1:637~643.
Juge-Aubry CE, Hammar E, Siegrist-Kaiser C, Takeshita A, Chin WW, Burger AG, Meier CA, Hammar E. 1999. Regulation of the transcriptional activity of the peroxisome proliferator-activated receptor alpha by phosphorylation of a ligand-independent transactivating domain [J]. J Biol Chem, 274: 10505~10510.
Kang ES, Hur KY, Cha BS, Lee HJ, Kim HJ, Shim WS, Ahn CW, Kim SH, Lee HC. 2006. The 11482GNA polymorphism in the perilipin gene is associated with weight gain with rosiglitazone treatment in type 2 diabetes [J]. Diabetes Care, 29: 1320~1324.
Kanno K, Wu MK, Scapa EF, Roderick SL, Cohen DE. 2007. Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2 [J]. Biochim. Biophys. Acta, 1771: 654~662. Kast-Woelbern HR, Dana SL, Cesario RM, de Grandpre LY, Brooks ME, Osburn DL, Reifel-Miller A,
Klausing K, Leibowitz MD. 2004. Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis [J].Biol Chem, 279(23): 908~915.
Ke Y, Qiu J, Ogus S, Shen WJ, Kraemer FB, Chehab FF. 2003. Overexpression of leptin in transgenic mice leads to decreased basal lipolysis, PKA activity, and perilipin levels [J]. Biochem Biophys Res Commun, 312: 165~1170.
Kern PA, Di Gregorio G, Lu T, Rassouli N, Ranganathan G. 2004. Perilipin expression in human adipose tissue is elevated with obesity [J]. J Clin Endocrinol Metab, 89: l352~1358.
Kim H, Jung T, Kang E, Kim D, Ahn C, Lee K, Lee H, Cha B. 2007. Depot-specific regulation ofperilipin by rosiglitazone in a diabetic animal model [J]. Metabolism, 56 (5): 676~685.
Kim SE, Park JH ,Cho YW, Chung H, Jeong SY, Lee EB and Kwon IC. 2003. Porous chitosan scaffold containing microspheres loaded with transforming growth factor-betal: implications for cartilage tissue engineering [J]. J Control Release, 91(3): 365.
Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM. 2007. A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity [J]. Science, 315: 525~528.
Koh EH, Kim MS, Park JY, Kim HS , Youn JY, Park HS, Youn JH, and Lee KU . 2003. Peroxisome proliferator-activated receptor (PPAR)-alpha activation prevents diabetes in OLETF rats: comparison with PPAR-gamma activation [J]. Diabetes, 52: 2331~ 2337.
Korhonen S, Heinonen S, Hiltunen M , Helisalmi S, Hippel?inen M, Koivunen R, Tapanainen JS andLaakso M. 2003. Polymorphism in the peroxisome proliferators-activated receptor gamma gene in women with polycystic ovary syndrome [J]. Hum Reprod, 18(3): 540~543.
Kota BP, Huang TH, Roufogalis BD. 2005. An overview on biological mechanisms of PPARs [J]. harmacol Res, 51(2): 85~94.
Kuenzli S, Saurat JH. 2003. Peroxisome proliferator-activated receptors in cutaneous biology [J].Br J Dermatol, 149(2): 229~236.
Lacquemoat C, Lepretre F, Pinend Torre I. 2000. Mutation sequencing of the PPARαgene in type2 diabetes association with coronary heart disease [J]. Diabetes & Metabolism, 26(4): 393.
Lapsys NM, Kriketos AD, Lim Fraser M, Poynten AM, Lowy A, Furler SM, Chisholm DJ, and Cooney GJ. 2000. Expression of genes involved in lipid metabolism correlate with peroxisome proliferators activated receptor gamma expression in human skeletal muscle [J].J Clin Endocrinol Metab, 85: 4293 ~ 4297.
Lazar MA. 2005. PPAR gamma, 10 years later [J]. Biochimie, 87 (1): 9~13.
Lazennec G, Canaple L, Saugy D. 2000. Activation of Peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators [J]. Mol Endoccninnol, 14(12): 1962.
Lazennec G, Canaple L, Saugy D, Walter Wahli. 2000. Activation of peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators [J]. Mol Endocrinol, 14: 1962~1975.
Lee CH, Olson P, Hevener A, Isaac M, Chong LW, Olefsky JM, Gonzalez FJ, Ham J, Kang H, Peters JM, and Evans RM. 2006. PPAR delta regulates glucose metabolism and insulin sensitivity [J].Proc Natl Acad sci USA, 103: 3444~3449.
Lee MS, Kliewer SA, Procencal J, Wright PE, Evans RM. 1993. Structure of the retinoid X receptor alpha DNA binding domain: a helix required for homodimeric DNA binding. Science, 260: 1117-1121.
Lee SS, Cgan WY, Lock, Wan DC, Tsang DS, Cheung WT. 2004. Requirement of PPAR alpha in maintaining phospholipids and triacylglycerol homeostasis during energy deprivation [J].J Lipid Res, 45(11): 2025~2037.
Lefebvre P, Chlinetti G, Fruchart JC, and Bart S. 2006. Sorting out the roles of PPARαin energy metabolism and vascular homeostasis [J]. J Clin Invest, 116(3): 571~580.
Londos C, Brasaemle DL, Schultz CJ, Adler-Wailes DC, Levin DM, Kimmel AR, Rondinone CM. 1999. On the control of lipolysis in adipocytes [J]. Ann N Y Acad Sci, 892: 155~168.
Luz Ibarra-Lara , Luz G. Cervantes-Pérez a, Francisca Pérez-Severiano, Leonardo Del Valle, EstherRubio-Ruiz , Elizabeth Soeria-Castro, Gustavo S Pastelin-Hernandez, María Sanchez-Aguilar, Juan C Martrnez-Lazcano, Alicia Sanchez-Mendoza. 2010. PPARαstimulation exerts a blood pressure lowering effect through different mechanisms in a time-dependent manner [J]. European Journal of Pharmacology, 627: 185~193.
Mahoney DJ, Parise G, Melov A, Safdar SA, and Tarnopolsky MA. 2005. Analysis of global mRNA expression in humans keletal muscle during recovery form endurance exercise [J]. FASEBJ, 9: 1498~1500.
Marcinkiewicz A, Gauthier D, Garcia A, Brasaemle DL. 2006. The phosphorylation of serine 492 of perilipin a directs lipid droplet fragmentation and dispersion [J]. J Biol Chem, 281 (17): 11901~11909.
María del Carmen González, J. Christopher Corton, Herrera E, Bocos C. 2009. Peroxisome proliferator-activated receptor-α(PPARα) agonists down-regulatesα2-macroglobulin expression by a PPARα-dependent mechanism [J]. Biochimie, 91: 1029~1035.
Marx N, Duez H, Fruchart JC, Staels B. 2004. Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells [J]. Circ Res, 4(9): 1168~1178.
Michalil L, Desvergne B, Wahli W. 2004. Peroxisome proliferator-activated receptor and cancers: complex stories [J]. Nat Rev Cancer, 4: 61~70.
Michung Yoon. 2009. The role of PPARαin lipid metabolism and obesity: Focusing on the effects of estrogen on PPARαactions [J]. Pharmacological Research, 60: 151~159.
Min-Jeong Shin, Alka M. Kanaya, Ronald M. Krauss. 2008. Polymorphisms in the peroxisome proliferator activated receptorαgene are associated with levels of apolipoprotein CIII and triglyceride in African-Americans but not Caucasians [J]. Atherosclerosis, 198: 313~319.
Miyoshi H, Perfield JW 2nd, Souza SC, Shen WJ, Zhang HH, Stancheva ZS, Kraemer FB, Obin MS, Greenberg AS. 2007. Control of adipose triglyceride lipase action by serine 517 of perilip in A globally regulates protein kinase A-stimulated lipolysis in adipocytes [J]. J Biol Chem, 282 (2): 996~1002.
Mooney RA, Bordwell KL. 1991. Counter-regulation by insulin and isoprenaline of a prominent fat-associated phosphoprotein doublet in rat adipocytes [J]. Biochem J, 274 (Pt2):433~438.
Mori H, Ikegami H , Kawaguchi Y , Seino S , Yokoi N , Takeda J , Inoue I , Seino Y , Yasuda K , Hanafusa T, Yamagata K , Awata T , Kadowaki T , Hara K , Yamada N , Gotoda T, Iwasaki N , Iwamoto Y, Sanke T, Nanjo K, Oka Y, Matsutani A, Maeda E and Kasuga1 M. 2001. The Pro12→Ala substitution in PPARγis associated with resistance to development of diabetes in the general populatins: possible involvement in impairment of insulin secretion in individuals with type2 diabetes [J]. Diabetes, 50(4): 891 ~ 894.
Mossner R, Kaiser R,Matern P, Krüger U, Westphal G, Brockm?ller J, Ziegler A , Neumann C, K?nig IR and Reich K. 2004. Variations in the genes encoding the peroxisome proliferator-activated receptorsαandγin psoriasis [J]. Arch Dermatol Res, 296(1):1~5.
Mottagui-Tabar S, Ryden M, Lofgren P, Faulds G, Hoffstedt J, Brookes AJ, Andersson I, Arner P. 2003. Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis [J]. Diabetologia, 46: 789~797.
Mynatt RL, Stephens JM. 2001.Agouti regulates adipocyte transcription factors[J]. Am J Physiol Cell Phusiol, 2001, 280(4): C 954~961
Nagai S, Shimizu C , Umetsu M, Umetsu M, Taniguchi S, Endo M, Miyoshi H, Yoshioka N, Kubo M, and Koike T. 2004. Identification of a functional peroxisome proliferator-activated receptor responsiveelement within the murine perilinp in gene [J]. Endocrinology, 145 (5): 2346~2356.
Neve BP, Fruchart JC, Staels B. 2000. Role of the peroxisome proliferator-activated receptors (PPARs) in atherosclerosis [J]. Biochemical Pharmacology, 60: 1245~1250.
Nishiu J, Tanaka T, Nakamura T. 1998. Isolation and chromosomal mapping of the human homolog of perilipin (PLIN), a rat adipose tissue-specific gene, by differential display method [J]. Genomcis, 48 (2): 254~257.
Olefsky JM. 2000. Treatment of insulin resistance with peroxisome proliferator- activated receptor- gamma agonist [J]. J Clin Invest, 106(4): 467~472.
Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM. 2001. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport [J].Proc Natl Acad Sci USA, 98: 5306~5311.
Orio Jr F, Matarese G, Biase S Di, Palomba S, Labella D, Sanna V, Savastano S, Zullo F, Colao A and Lombardi G. 2003. Exon6 and 2 peroxisome proliferators- activated receptor gamma polymorphism in polycystic ovary syndrome [J]. J Clin Endocrinol Metab, 88(12): 5887~5892.
Orita M, Suzuki Y, Sekiya T, Hayashi K. 1989. Rapid and sensitive detection of mutations and DNA polymorphisms using the polymerase chain reaction [J]. Genomics, 5: 8741.
Orita M, Suzuki Y, Swkiya T, Hayashi K. 1989. Rapid and sensitive detection of point mutations and genetic polymorphism using polymerase chain reaction [J]. Genomics, 5: 874~879.
Park SY, Pajvani U, McCormack FX, Kim HJ, Higashimori T, Hong EG, Lee MK, Danton C, Deshmukh S, Cline GW, Wu JJ, Bennett AM, Rothermel B, Kalinowski A, Russell KS, Kim YB, Kelly DP, Kim JK. 2005. Cardiac-specific overexpression of peroxisome proliferator-activated receptor-αcauses insulin resistance in heart and 1iver [J]. Diabetes, 54: 2514~2524
Peng DQ, Zhao SP, Nie S, Li J. 2003. Gene-gene interaction of PPARg and ApoE affects coronary heart disease risk [J]. International Journal of Cardiology, 92: 257~263.
Perez-Martinez P, Yiannakouris N, Lopez-Miranda J, Arnett D, Tsai M, Galan E, Straka R, Delgado- Lista J, Province M, Ruano J, Borecki I, Hixson J, Garcia-Bailo B, Perez-Jimenez F, Ordovas JM. 2008. Postprandial triacylglycerol metabolism is modified by the presence of genetic variation at the perilipin (PLIN) locus in 2 white populations [J]. Am J Clin Nutr, 87 (3): 744~752.
Peters JM, Lee SST, Li W, Wen L, Jerrold M. Ward, Gavrilova O, Everett C, Reitman ML, Hudson LD, and Gonzalez FJ. 2000. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptorβ(δ) [J]. Mol Cell Biol, 20(14): 5119~5128.
Peters JM, Yokota T, Vasseur F, Fievet C, Gonzalez FJ. Auwerx J, Hennuyer N. 1997. Altemtions in hpoprotein metabohsm in peroxisome proliferators-activated receptorα-deficient mice [J]. J Biol Chem, 272: 27307~27312.
Picard F, Auwerx J. 2002. PPAR (gamma) and glucose homeostasis [J]. Annu Rev Nutr, 22:167~197.
Pishva H, Mahboob S, Mehdipour P, Eshraghian M, Mohammadi-Asl J, Hosseini S, Rahmany M. 2009. Association between the FABP2 Ala54Thr, PPARa Leu162/Val, and PPARa intron7 polymorphisms and blood lipids ApoB and ApoCIII in hypertriglyceridemic subjects in Tehran [J]. Journal of Clinical Lipidology, 3: 187~194.
Plutzky J. 2003. PPARs as therapeutic targents: reverse cardiology? [J]. Science, 302: 406~407.
Qi L, Corella D, Sorli J V, Portoles O, Shen H, Coltell O, Godoy D, Greenberg AS, J Ordovas M. 2004. Genetic variation at the perilipin (PLIN) locus is associated with obesity-related phenotypes in White women [J]. Clin Genet, 66299~310.
Qi L, Shen H, Larson I, Schaefer EJ, Greenberg AS, Tregouet DA, Corella D, Ordovas JM. 2004. Gender-specific association of a perilipin gene haplotype with obesity risk in a white population [J]. Obes Res, 12: 1758~1765.
Qi L, Tai E S, Tan C E, Shen H, Chew S K, Greenberg A S, Corella D, Ordovas J M. 2005. Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population [J]. J. Mol. Med., 83: 448~456.
Qi L, Zhang CL, Greenberg A, Hu FB. 2008. Common variations in perilipin gene, central obesity, and risk of type 2 diabetes in US women [J]. Obesity, 16: 1061~1065.
Qu S,Su D,Altomonte J, Kamagate A, He J, Perdomo G, Tse T, Jiang Y, and Dong HH. 2007.PPAR｛alpha｝mediates the hypolipidemic action of fibrates by antagonizing FoxO1 [J]. American Journal of Physiology-Endocrinology and Metabolism, 292(2): E421~434.
Rangwala SM, hazar MA. 2004. Peroxisome proliferator-activated receptor gamma in diabetes and metabolism [J]. Trends Pharmacol Sci, 25(6):331~336.
Reddy. 2001. Nonalcoholic steatosis and steatohepatitisⅢperoxisomal beta-oxidation, PPAR alpha, and steatohepatitis [J].Am J Physiol Gastrointest Liver Physiol, 281(6): G1333~G1339.
Ren XD, Lu YQ, Ye KH. 2005. The antitumor molecular machnisms of non steroid anti-inflammatory drugs [J]. Chin Pharmacol Bull, 21: 527~531.
Ricote M, Glass CK. 2001. New roles for PPARs in cholesterol homeostasis [J].Trends Pharmacol Sci, 22(9): 441~443: discussion 444.
Rieck M, Wedeken L, Muller-Brusselbach S, Meissner W and Müller R. 2007. Expression level and agonist-binding affect the turnover, ubiquitination and complex formation of peroxisome proliferator- activated receptor-β[J]. FEBSJ, 274: 5068~5076.
Ristow M, Muller-Wieland D, Pfeiffer A, Krone W, Kahn CR.1998. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation [J]. N Engl J Med, 339 (14): 953 - 959.
Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM. 2002. C/EBP- alpha induces adipogenesis through PPARgamma: a unified pathway [J]. Genes Dev, 16(1): 22~26.
Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. 1999. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro [J].Mol Cell, 4 (4): 611~617.
Rotimi CN, Comuzzie AG, Lowe WL, Luke A, Blangero J, Cooper RS. 1999. The quantitative trait locus on chromosome 2 for serum leptin levels is confirmed in African-Americans [J]. Diabetes, 48: 643~644.
Samir Ben Ali , Fatma Ben Yahia , Yousra Sediri, Amani Kallel , Bochra Ftouhi ,Moncef Feki, Monia Elasmi , Sameh Haj-Taieb , Omar Souheil , Haifa Sanhagi,Hedia Slimane b, Riadh Jemaa , Naziha Kaabachi. 2009. Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptorγ-2 gene on obesity risk and leptin levels in a Tunisian population [J]. Clinical Biochemistry, 42: 1642~1647.
Savage DB, Tan GD, Acerini CL, Jebb SA , Agostini M, Gurnell M , Williams RL , Umpleby AM,Louise Thomas E, Bell JD , Dixon AK , Dunne F , Boiani R , Cinti S , Vidal-Puig A , Karpe F, Krishna V, Chatterjee K and O’Rahilly S. 2003. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma [J]. Diabetes, 52: 910~ 917.
Scapa EF, Pocai A, Wu MK, Gutierrez-Juarez R, Glenz L, Kanno K, Li H, Biddinger S, Jelicks LA, Rossetti L, Cohen DE. 2008. Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2 [J]. FASEB J. 22: 2579~2590.
Schmidt A, Endo N, RutledgeS J, Vogel R, Shinar D, Rodan GA. 1992. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids [J]. Mol Endocrinol, 6: 1634~1641.
Seo YS, Kim JH, Jo NY, Choi KM, Baik SH, Park JJ, Kim JS, Byun KS, Bak YT, Lee CH, Kim A, Yeon JE. 2008. PPARagonists treatment is effective in a nonalcoholic fatty liver diseasr animal model by modulating fatty-acid metabolic enztmes [J]. J Gastrenterol Hepatol, 23(1): 102~109.
Shaw N, Elholm M, Noy N. 2003. Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptorβ/δ[J]. J Biol Chem, 278: 41589~41592.
Shin HD, Park BL, Kim LH, Cottel D, Lebel P, Dallongeville J, Deeb S, Auwerx J and Amouyel P. 2004. Genetic polymorphisms in peroxisome proliferator-activated receptorδassociate with obesity [J]. Diabetes, 53: 847~851.
Skogsberg J, McMahon A D, Karpe F, Hamsten A, Packard C J & Ehrenborg E. 2003. Peroxisome proliferators activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men [J]. J Intern Med, 254: 597~604
Soenen S, Mariman EC, Vogels N, Bouwman FG, den Hoed M, Brown L, Westerterp-Plantenga MS. 2009. Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance [J]. Physiology & Behavior, 96: 723~728.
Souza SC, de Vargas LM, Yamamoto MT, Lien P, Franciosa MD, Moss LG, Greenberg AS. 1998. Overexpression of perilipin A and B blocks the ability of tumor necrosis factor alpha to increase lipolysis in 3T3-L1 adipocyte [J]. J Biol Chem, 273(38): 24665~4669
Subramanian V, Garcia A, Sekowski A, Brasaemle D L. 2004. Hydrophobic sequences target and anchor perilipin A to lipid droplets [J]. J Lipid Res, 45 (11): 1983~1991.
Sundvold H, Brzozowska A, and Lien S. 1997. Characterization of bovine peroxisome proliferator- activated receptors gamma 1 and gamma 2: genetic mapping and differential expression of the two isoforms [J]. Biochem. Biophys. Res. Commun. 239 (3): 857~861.
Sztalryd C, Xu G, Doward H, Tansey JT, Contreras JA, Kimmel AR, and Londos C. 2003. Perilipin A is essential for the translocation of Hormone-sensitive lipase during lipolytic activation [J]. J. Cell Biol, 161(6): 1011~1012.
Tahara T, Arisawa T, Shibata T, Nakamura M, Wang F, Maruyama N, Kamiya Y, Nakamura M, Fujita H, Nagasaka M, Iwata M, Takahama K, Watanabe M, Hirata I, Nakano H Nakamura M, Wang F, Maruyama N, Kamiya Y, Nakamura M, Fujita H, Nagasaka M, Iwata M, Takahama K, Watanabe M, Hirata I, Nakano H. 2008. Influence of Peroxisome Proliferator-activated Receptor (PPAR) gamma Plo12Ala Polymorphism as a Shared Risk Marker for Both Gastric Cancer and Impaired Fasting Glucose (IFG) in Japanese [J]. Dig Dis Sci, 53 (3): 614-621.
Tai ES, Demissie S, Cupples LA, corella D, Wilson PW, Schaefer EJ and Ordovas JM. 2002. Association between the PPARαL162V polymorphism and plasma lipid levels: The Framingham Offspring Study [J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 22(5): 805~811.
Takao K, Jing C, and Keith RM. 2001. Magnetic Bead-Isolated Single-Strand DNA for SSCP Analysis. In: Walker, John M. Methods in Molecular Biology [J]. Humana Press, 135~147.
Tanaka T, Yamamoto J, Iwasaki S, Asaba H, Hamura H, Ikeda Y, Watanabe M, Magoori K, Ioka RX, Tachibana K, Watanabe Y, Uchiyama Y, Sumi K, Iguchi H, Ito S, Doi T, Hamakubo T, Naito M, Auwerx J, Yanagisawa M, Kodama T, and Sakai J. 2003. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic Syndrome [J]. Proc Natl Acad sci USA, 100: 15924~15929.
Tanrori Y, Masugi J, Nishino N, Kasuga M. 2002. Role of peroxisome porliferator-activated receptor- gamma in maintenance of the characteristics of mature 3T3-L1 adipocytes [J]. Diabetes, 51(7): 2045~2055.
Tansey JT, Huml AM, Vogt R, Davis KE, Jones JM, Fraser KA, Brasaemle DL, Kimmel AR, and Londos C. 2003. Functional studies on native and mutated forms of perilipin. A role in protein kinase A-mediated lipolysis of triacylglycerols in Chinese hamster ovary cells [J]. J Biol Chem, 278(10): 8401~ 8406.
Tansey JT, Sztalryd C, Gruia-Gray J, Roush DL, Zee JV, Gavrilova O, Reitman ML, Deng CX, Li C, Kimmel AR, Londos C. 2001. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production , and resistance to diet-induced obesity [J]. J PNAS, 98 (11): 6494~6499.
Thomas Lunda?sen, Mary C. Hunt, Lisa-Mari Nilsson Sabyasachi Sanyal, Bo Angelin, Stefan EH. Alexsonc and Mats Rudling. 2007. PPARa is a key regulator of hepatic FGF21 [J]. Biochemical and Biophysical Research Communications, 360: 437~440.
Tontonoz P, Hu E, Spiegelman B M. 1994. Stimulation of adipogenesis in fibroblasts by PPAR gamma2, a lipid-activated transcription factor [J]. Cell, 79 (7): 1147~1156.
Tontonoz P, Hu E, Spiegelman B. 1995. M. Regulation of adipocyte gene expression and differentiation peroxisome porliferator activated receptor gamma [J]. Curr Opin Genet Dev, 5 (5):571~576.
Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM. 1998. PPARgamma promotes monocyte /macrophage differentiation and uptake of oxidized LDL [J]. Cell, 93(2): 241~252.
Tontonoz P, Singer S, Forman B M, Sarraf P, Fletcher JA, Fletcher CD, Brun RP, Mueller E, Altiok S, Oppenheim H, Evans RM, Spiegelman BM. 1997. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferators-activated receptorγand the retinoid X receptor [J]. Proc Natl Acad Sci USA, 94: 237~241.
Toshihide Kawai, Maggie C.Y. Ng a, M. Geoffrey Hayes, Issei Yoshiuchi, Takafumi Tsuchiya, Heather Robertson, Nancy J. Cox , Kenneth S. Polonsky,Graeme I. Bell, David A. Ehrmann. 2009. Variation in the perilipin gene (PLIN) affects glucose and lipid metabolism in non-Hispanic white women with and without polycystic ovary syndrome [J]. Diabetes research and clinical practice, 186~192.
Tsunoda M, Kobayashi N, Ide T, Utsumi M, Nagasawa M, Murakami K.2008. A novel PPAR agonist ameliorates insulin resistance in dogs fed a high-fat diet [J]. Am J Physiol Endocrinol Metab, 294: E833-E840.
Uppenberg J, Svensson C, Jaki M, Bertilsson G, Jendeberg L, Berkenstam A. 1998. Crystal structureof the ligand binding domain of the human nuclear receptor PPARgamma. J Biol Chem, 273(47): 31108 ~31112.
Vanden Heuvel JP. 2007. The PPAR resource page [J].Bio Chim Biophys Acts, 1771(8): 1108 ~1112.
Vantitnen M, Nuutifa P, Kuulasmaa T, Pihlajam?ki J, H?llsten K, Virtanen K A, Lautam?ki R, Peltoniemi P, Takala T, Antti P.M. Viljanen, Knuuti J and Markku Laakso. 2005. Single nucleotide polymorphisms in the peorxisome proliferator-acitvated receptorδgene are associated with skeletal muscle glucose uptake [J].Diabetes, 54: 3587~3591.
Vohl MC, Lepage P, Gaudet D. 2000. Molecular-scanning of the human PPARαgene: association of the L162V mutation with hyperapobtali protein in emia [J]. J Lipid Res, 41(6):945~952.
Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. 2003. Peroxisome proliferator-activated receptor delta activates fat etabolism to prevent obesity [J]. Cell, 113: 159~170.
Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, Bayuga-Ocampo CR , Ham J , Kang H, Evans R M . 2004. Regulation of muscle fiber type and running endurance by PPAR delta [J]. P1oS Biol, 2(10): e294.
Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM. 1999. Cross-regulation of C /EBP Alpha and PPAR Gamma Controls the Transcrip tional Pathway of Adipogenesis and Insulin Sensitivity [J]. Journal of Molecular and Cellular Cardiology, 3: 151 ~158.
Yamada Y, Ando F, Shimokata H. 2006. Association of polymorphisms in forkhead box C2 and perilipin genes with bone mineral density in community-dwelling Japanese individuals [J]. Int. J. Mol. Med, 18: 119~127.
Yamakawa-Kobayashi K, Ishiguro H, Arinami T, Miyazaki R, Hamaguchi H. 2002. A Val 227 Ala polymorphism in the peroxisome proliferator activated receptor alpha (PPAR alpha) gene is associated with variations in serum lipid levels [J]. Jed Genet, 39: 189~191.
Yang LL, Hua Q, Liu RK, and Yang Z. 2009. Association between two common polymorphisms of PPARγgene and metabolic syndrome families in a Chinese population [J]. Archives of Medical Research, 40: 89~96.
Ye P, Wang Z, Zhang XJ, Zhao YL. 2005. Age related decrease in expression of peroxisome proliferators activated receptorαand its effects on development of dyslipidemia [J]. Chin Med J (Engl), 118 (13): 1093~1098.
Yen CJ, Beamer BA, Negri C, Silverb K, Brownb KA, Yarnallc DP, Burnsc DK, Rotha J and Shuldinerb AR. 1977. Molecular scanning of the human peroxisome proliferators activated receptorγ(PPARγ) gene in diabetic Caucasians: identification of a Pro12Ala PPARγ2 missense mutation [J].Biochem Biophy Res Commun, 241: 270~274
Yiannakouris N, Yannakoulia M, Melistas L, Chan JL, Klimis-Zacas D and Mantzoros CS. 2001.The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of bodyweight and body composition variability [J]. J Clin Endocrinol Metab, 86(9): 4434~4439.
Yue Ji-Rong, Dong Bi-Rong, Huang Chang-Quan, Lu Zhen-Chan, Wu Hong-Mei, Zhang Yan-Ling, and Tod A. Mattis. 2009. Pro12Ala Polymorphism in PPARγ2 Associated with Depression in Chinese Nonagenarians/Centenarians [J].Archives of Medical Research, 40: 411~415.
Zhang B, Berger J, Zhou G, Elbrecht A, Biswas S, White-Carrington S, Szalkowski D, and Moller DE.1996. Insulin and mitogen activated protein kinase-mediated phosphorylation and activation of peroxisome proliferator-activated receptor gamma [J]. J Biol Chem, 271: 31771~31774.
Zhang HF, He YX, Chung PK, Tong TK, Fu FH, Chen YJ, Jiao GF. 2009. Effects of 12 weeks of exercise on hepatic TNF-αand PPARαin an animal model of high-fat diet-induced nonalcoholic steatohepatitis [J]. J Exerc Sci Fit, 7 (1): 18~23.