PPARγ在动物脂肪发育中的研究进展
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摘要
脂肪是动物体内主要的能量贮存形式。过氧化物酶体增殖物激活受体γ(PPARγ)属于核受体超家族成员,在脂肪代谢过程中发挥重要的调节功能。PPARγ包括4种亚型结构,其中仅PPARγ1和PPARγ2在脂肪组织中表达。PPARγ在脂肪细胞分化和脂质代谢过程中起关键作用,其功能受多种转录因子(ZFP423、C/EBPs、KLFs等)的调节。文章通过对PPARs的结构特点、PPARγ在脂肪组织中的表达规律和分子作用机制进行综述,以期为深入了解脂肪组织的形成规律、改善肉品质提供理论依据。
Fat is the main form of energy storage in animals. The peroxisomal proliferator activation receptor γ(PPARγ) is a member of the nuclear receptor superfamily and plays an important regulatory role in the process of fat metabolism. PPARγ consists of four subtypes, of which only PPARγ1 and PPARγ2 are expressed in adipose tissue. PPARγ plays a key role in adipocyte differentiation and lipid metabolism, and its function is regulated by various transcription factors(ZFP423, C/EBPs, KLFs, etc.). This article reviewed the structural characteristics of PPARs, PPARγ expression in adipose tissue and molecular mechanism, for understanding the formation law of adipose tissue, and provide theoretical basis to improve meat quality.
Fat is the main form of energy storage in animals. The peroxisomal proliferator activation receptor γ(PPARγ) is a member of the nuclear receptor superfamily and plays an important regulatory role in the process of fat metabolism. PPARγ consists of four subtypes, of which only PPARγ1 and PPARγ2 are expressed in adipose tissue. PPARγ plays a key role in adipocyte differentiation and lipid metabolism, and its function is regulated by various transcription factors(ZFP423, C/EBPs, KLFs, etc.). This article reviewed the structural characteristics of PPARs, PPARγ expression in adipose tissue and molecular mechanism, for understanding the formation law of adipose tissue, and provide theoretical basis to improve meat quality.
引文
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[3] ZENG Z Y, LIAO G H, L Y F, et al. Research progress of PPARs agonists on cardiovascular and cerebrovascular diseases[J]. J Med Chem, 2014, 24(2):147-156.
[4] ABDULJABBAR R, ALKAABI M M, NEGM O H, et al. Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer[J]. Food Chem Toxicol, 2015, 150(3):511-522.
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[6] MAZUMDER M, PONNAN P, DAS U, et al. Investigations on binding pattern of kinase inhibitors with PPARγ: molecular docking, molecular dynamic simulations, and free energy calculation studies[J]. PPAR Res, 2017, 2017:6397836.
[7] NEHER M D, WECKBACH S, HUBERLANG M S, et al. New insights into the role of peroxisome proliferator-activated receptors in regulating the inflammatory response after tissue injury[J]. PPAR Res, 2012, 2012(5):728461.
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[12] STEGER D J, GRANT G M, TOMARU T, et al. Propagation of adipogenic signals through an epigenomic transition state[J]. Water Res, 2010, 24(10):1035-1044.
[13] SCHMIDT S F, J∅RGENSEN M, YUN C, et al. Cross species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites[J]. BMC Psychiatry, 2011, 12(1):152.
[14] LI G, YAO W, JIANG H. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue[J]. J Nutr, 2014, 144(12):1887.
[15] 樊月圆. 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[D].杨凌:西北农林科技大学, 2010.
[16] 盘道兴, 王振, 杨茂林,等. 不同品种猪PPARγ和C/EBPα基因表达规律与肌内脂肪含量的相关[J]. 中国农业科学, 2017, 50(1):171-182.
[17] 王丽, 那威, 王宇祥,等. 鸡PPARγ基因的表达特性及其对脂肪细胞增殖分化的影响[J]. 遗传, 2012, 34(4):454-464.
[18] ALICE L K, LEI S. Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes[J]. Mar Pollut Bull, 2013, 33(5):711-719.
[19] RAJAKUMARI S, WU J, ISHIBASHI J, et al. EBF2 determines and maintains brown adipocyte identity[J]. Dig Surg, 2013, 17(4):562-574.
[20] CHANG J S, HA K. A truncated PPAR gamma 2 localizes to mitochondria and regulates mitochondrial respiration in brown adipocytes[J]. PLoS One, 2018, 13(3):e0195007.
[21] KRONE W J A, STEGEHUIS F, KONINGSTEIN G, et al. PPAR gamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein[J]. Eur J Med Chem, 2012, 15(3):395.
[22] PETROVIC N, WALDEN T B, SHABALINA I G, et al. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocyte[J]. J Biol Chem, 2010, 285(10):7153.
[23] CHOI S H, CHUNG K Y, JOHNSON B J, et al. Co-culture of bovine muscle satellite cells with preadipocytes increases PPARγ and C/EBPβ gene expression in differentiated myoblasts and increases GPR43 gene expression in adipocytes[J].J Nutr Biochem, 2013, 24(3):539-543.
[24] WU J, BOSTRÖM P, SPARKS L M, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human[J]. Cell, 2012, 150(2):366-376.
[25] GUPTA R K, ARANY Z, SEALE P, et al. Transcriptional control of preadipocyte determination by Zfp423[J]. Nature, 2010, 464(7288):619-623.
[26] LI S F, GUO L, QIAN S W, et al. G9a is transactivated by C/EBPbeta to facilitate mitotic clonal expansion during 3T3-L1 preadipocyte differentiation[J]. Am J Physiol Endocrinol Metab, 2013, 304(9):E990-E998.
[27] LEE J, OZCAN U. Unfolded protein response signaling and metabolic diseases[J]. J Biol Chem, 2014, 289(3):1203-1211.
[28] YU K, MO D, WU M, et al. Activating transcription factor 4 regulates adipocyte differentiation via altering the coordinate expression of CCATT/enhancer binding protein β and peroxisome proliferator-activated receptor γ[J]. FEBS J, 2014, 281(10):2399-2409.
[29] JIANG S, WEI H, SONG T, et al. KLF13 promotes porcine adipocyte differentiation through PPARγ activation[J]. Biochem Pharmacol, 2015, 5(1):28.
[30] RAJAKUMARI S, WU J, ISHIBASHI J, et al. EBF2 determines and maintains brown adipocyte identity[J]. Eur J Med Chem, 2013, 17(4):562-574.
[31] FREISE C, TROWITZSCH-KIENAST W, ERBEN U, et al. (+)-Episesamin inhibits adipogenesis and exerts anti-inflammatory effects in 3T3-L1 (pre)adipocytes by sustained Wnt signaling, down-regulation of PPARγ and induction of iNOS[J]. J Nutr Biochem, 2013, 24(3):550-555.
[32] CHUNG S S, LEE J S, KIM M, et al. Regulation of Wnt/β-catenin signaling by CCAAT/enhancer binding protein β during adipogenesis[J]. Obesity, 2012, 20(3):482-487.
[33] OLOKPA E, MOSS P E, STEWART L V. Crosstalk between the androgen receptor and PPAR gamma signaling pathways in the prostate[J]. PPAR Res, 2017, 2017(2):9456020.
[2] SIERSB ÆK R, NIELSEN R, MANDRUP S. Transcriptional networks and chromatin remodeling controlling adipogenesis[J]. Trends Endocrinol Metab, 2012, 23(2):56-64.
[3] ZENG Z Y, LIAO G H, L Y F, et al. Research progress of PPARs agonists on cardiovascular and cerebrovascular diseases[J]. J Med Chem, 2014, 24(2):147-156.
[4] ABDULJABBAR R, ALKAABI M M, NEGM O H, et al. Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer[J]. Food Chem Toxicol, 2015, 150(3):511-522.
[5] MENENDEZGUTIERREZ M P, ROSZER T, RICOTE M. Biology and therapeutic applications of peroxisome proliferator- activated receptors[J]. Curr Top Med Chem, 2012, 12(6):548-584.
[6] MAZUMDER M, PONNAN P, DAS U, et al. Investigations on binding pattern of kinase inhibitors with PPARγ: molecular docking, molecular dynamic simulations, and free energy calculation studies[J]. PPAR Res, 2017, 2017:6397836.
[7] NEHER M D, WECKBACH S, HUBERLANG M S, et al. New insights into the role of peroxisome proliferator-activated receptors in regulating the inflammatory response after tissue injury[J]. PPAR Res, 2012, 2012(5):728461.
[8] POULSEN L L C, SIERSBÆK M, MANDRUP S. PPARs: fatty acid sensors controlling metabolism[J]. Semin Cell Dev Biol, 2012, 23(6):631.
[9] 杨谷良, 潘敏雄, 向福,等. PPARγ调控脂肪细胞增殖和分化机理研究进展[J]. 食品科学, 2017, 38(3):254-260.
[10] GARCíA-ROJAS P, ANTARAMIAN A, GONZÁLEZ-DÁVALOS L, et al. Induction of peroxisomal proliferator-activated receptor [gamma] and peroxisomal proliferator-activated receptor [gamma] coactivator 1 by unsaturated fatty acids, retinoic acid, and carotenoids in preadipocytes obtained from bovine white adipose tissue1,2[J]. J Anim Sci, 2010, 88(5):1801-1808.
[11] XU S, XU X. Research advances in the correlation between peroxisome proliferator-activated receptor-γand digestive cancers[J]. PPAR Res, 2018, 2018(2):1-7.
[12] STEGER D J, GRANT G M, TOMARU T, et al. Propagation of adipogenic signals through an epigenomic transition state[J]. Water Res, 2010, 24(10):1035-1044.
[13] SCHMIDT S F, J∅RGENSEN M, YUN C, et al. Cross species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites[J]. BMC Psychiatry, 2011, 12(1):152.
[14] LI G, YAO W, JIANG H. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue[J]. J Nutr, 2014, 144(12):1887.
[15] 樊月圆. 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[D].杨凌:西北农林科技大学, 2010.
[16] 盘道兴, 王振, 杨茂林,等. 不同品种猪PPARγ和C/EBPα基因表达规律与肌内脂肪含量的相关[J]. 中国农业科学, 2017, 50(1):171-182.
[17] 王丽, 那威, 王宇祥,等. 鸡PPARγ基因的表达特性及其对脂肪细胞增殖分化的影响[J]. 遗传, 2012, 34(4):454-464.
[18] ALICE L K, LEI S. Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes[J]. Mar Pollut Bull, 2013, 33(5):711-719.
[19] RAJAKUMARI S, WU J, ISHIBASHI J, et al. EBF2 determines and maintains brown adipocyte identity[J]. Dig Surg, 2013, 17(4):562-574.
[20] CHANG J S, HA K. A truncated PPAR gamma 2 localizes to mitochondria and regulates mitochondrial respiration in brown adipocytes[J]. PLoS One, 2018, 13(3):e0195007.
[21] KRONE W J A, STEGEHUIS F, KONINGSTEIN G, et al. PPAR gamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein[J]. Eur J Med Chem, 2012, 15(3):395.
[22] PETROVIC N, WALDEN T B, SHABALINA I G, et al. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocyte[J]. J Biol Chem, 2010, 285(10):7153.
[23] CHOI S H, CHUNG K Y, JOHNSON B J, et al. Co-culture of bovine muscle satellite cells with preadipocytes increases PPARγ and C/EBPβ gene expression in differentiated myoblasts and increases GPR43 gene expression in adipocytes[J].J Nutr Biochem, 2013, 24(3):539-543.
[24] WU J, BOSTRÖM P, SPARKS L M, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human[J]. Cell, 2012, 150(2):366-376.
[25] GUPTA R K, ARANY Z, SEALE P, et al. Transcriptional control of preadipocyte determination by Zfp423[J]. Nature, 2010, 464(7288):619-623.
[26] LI S F, GUO L, QIAN S W, et al. G9a is transactivated by C/EBPbeta to facilitate mitotic clonal expansion during 3T3-L1 preadipocyte differentiation[J]. Am J Physiol Endocrinol Metab, 2013, 304(9):E990-E998.
[27] LEE J, OZCAN U. Unfolded protein response signaling and metabolic diseases[J]. J Biol Chem, 2014, 289(3):1203-1211.
[28] YU K, MO D, WU M, et al. Activating transcription factor 4 regulates adipocyte differentiation via altering the coordinate expression of CCATT/enhancer binding protein β and peroxisome proliferator-activated receptor γ[J]. FEBS J, 2014, 281(10):2399-2409.
[29] JIANG S, WEI H, SONG T, et al. KLF13 promotes porcine adipocyte differentiation through PPARγ activation[J]. Biochem Pharmacol, 2015, 5(1):28.
[30] RAJAKUMARI S, WU J, ISHIBASHI J, et al. EBF2 determines and maintains brown adipocyte identity[J]. Eur J Med Chem, 2013, 17(4):562-574.
[31] FREISE C, TROWITZSCH-KIENAST W, ERBEN U, et al. (+)-Episesamin inhibits adipogenesis and exerts anti-inflammatory effects in 3T3-L1 (pre)adipocytes by sustained Wnt signaling, down-regulation of PPARγ and induction of iNOS[J]. J Nutr Biochem, 2013, 24(3):550-555.
[32] CHUNG S S, LEE J S, KIM M, et al. Regulation of Wnt/β-catenin signaling by CCAAT/enhancer binding protein β during adipogenesis[J]. Obesity, 2012, 20(3):482-487.
[33] OLOKPA E, MOSS P E, STEWART L V. Crosstalk between the androgen receptor and PPAR gamma signaling pathways in the prostate[J]. PPAR Res, 2017, 2017(2):9456020.