PPARγ调控脂肪细胞增殖和分化机理研究进展
|
摘要
随着人们生活水平的提高,长期摄取高热量的饮食,加上运动量不足,会造成身体能量过度累积,能量以脂肪的形式贮存,从而导致肥胖。早在1997年,世界卫生组织已经正式将肥胖列为一种慢性疾病。过氧化物酶体增殖物激活受体(peroxisome proliferators-activated receptors,PPARs)通过与靶基因启动子区调控序列结合,调控脂肪的代谢和脂肪细胞的增殖与分化。了解PPARs的结构特征、表达特性和作用机理等,对于控制肥胖及其引起的一系列疾病,具有重要的理论意义和实用价值。本文从PPARγ的结构特征和表达特点、配体对PPARγ的活化、PPARs间的相互作用、PPARγ在脂类代谢中的作用和天然配体对脂肪细胞的分化等进行综述,并从PPARγ调控脂肪细胞增殖的角度,提出了预防肥胖的对策。
With the improvement of living standards, long-term consumption of high calorie diet and physical inactivity result in storage of excess energy in the body in the form of fat, leading to obesity. Obesity has been officially listed as a chronic disease by the World Health Organization(WTO) in 1997. Peroxisome proliferator-activated receptors(PPARs) regulate the proliferation and differentiation of adipocytes by binding themselves with the trans-acting element of the target gene. Understanding the structural features, expression characteristics and mechanism of PPARs is of important theoretical significance and practical value for the control of obesity and related diseases. This article reviews the protein structure, gene expression and ligand activation of PPARγ, the interaction between different types of PPARs, and the role of PPARγ in lipid metabolism and the differentiation of adipocytes by natural ligands. Strategies for the prevention of obesity are put forward based on adipocyte proliferation regulation by PPARg.
With the improvement of living standards, long-term consumption of high calorie diet and physical inactivity result in storage of excess energy in the body in the form of fat, leading to obesity. Obesity has been officially listed as a chronic disease by the World Health Organization(WTO) in 1997. Peroxisome proliferator-activated receptors(PPARs) regulate the proliferation and differentiation of adipocytes by binding themselves with the trans-acting element of the target gene. Understanding the structural features, expression characteristics and mechanism of PPARs is of important theoretical significance and practical value for the control of obesity and related diseases. This article reviews the protein structure, gene expression and ligand activation of PPARγ, the interaction between different types of PPARs, and the role of PPARγ in lipid metabolism and the differentiation of adipocytes by natural ligands. Strategies for the prevention of obesity are put forward based on adipocyte proliferation regulation by PPARg.
引文
[1]DUVAL C,CHINETTI G,TROTTEIN F,et al.The role of PPARs in atherosclerosis[J].Trends in Molecular Medicine,2002,8(9):422-430.
[2]GUAN Y.Targeting peroxisome proliferator-activated receptors(PPARs)in kidney and urologic disease[J].Minerva Urologica e Nefrologica,2002,54(2):65-79.
[3]CHINETTI G,FRUCHART J C,STAELS B.Peroxisome proliferatoractivated receptors(PPARs):nuclear receptors at the crossroads between lipid metabolism and inflammation[J].Inflammation Research,2000,49(10):497-505.
[4]REDDY J K.Peroxisome proliferators and peroxisome proliferatoractivated receptorα[J].The American Journal of Pathology,2004,164(6):2305-2321.
[5]KERSTEN S,DESVERGNE B,WAHLI W.Roles of PPARs in health and disease[J].Nature,2000,405:421-424.DOI:10.1038/35013000.
[6]MORAES L A,PIQUERAS L,BSSHOP-BAILEY D.Peroxisome proliferator-activated receptors and inflammation[J].Pharmacology&Therapeutics,2006,110(3):371-385.DOI:10.1016/j.pharmthera.2005.08.007.
[7]ISSEMANN I,GREEN S.Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators[J].Nature,1990,347:1155-1208.DOI:10.1038/347645a0.
[8]ABBOTT B D.Review of the expression of peroxisome proliferatoractivated receptors alpha(PPARα),beta(PPARβ),and gamma(PPARγ)in rodent and human development[J].Reproductive Toxicology,2009,27(3/4):246-257.DOI:10.1016/j.reprotox.2008.10.001.
[9]HSU M H,PALMER C N,SONG W,et al.A carboxyl terminal extension of the zinc finger domain contributes to the specificity and polarity of peroxisome proliferator-activated receptor DNA binding[J].Journal of Biological Chemistry,1998,273(43):27988-27997.DOI:10.1074/jbc.273.43.279.
[10]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,2010:54-55.
[11]王丽,那威,王宇祥,等.鸡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(4):454-464.DOI:10.3724/SP.J.1005.2012.00454.
[12]GUO L,SUN B,SHANG Z,et al.Comparison of adipose tissue cellularity in chicken lines divergently selected for fatness[J].Poultry Science,2011,90(9):2024-2034.DOI:10.3382/ps.2010-00863.
[13]PETROVIC N,WALDEN T B,SHALINA I G et al.Chronic peroxisome proliferator-activated receptor gamma(PPARgamma)activation of epididymally derived whiteadipocyte cultures reveals a population of thermogenically competent,UCP1-containing adipocytes molecularly distinct from classic brown adipocytes[J].Journal of Biological Chemistry,2010,285(10):7153-7164.DOI:10.1074/jbc.M109.053942.
[14]CHOI S H,CHUNG K Y,JOHNSON B J,et al.Co-culture of bovine muscle satellite cells with preadipocytes increases PPARγand C/EBPβgene expression in differentiated myoblasts and increases GPR43 gene expression in adipocytes[J].Journal of Nutritional Biochemistry,2013,24(3):539-543.DOI:10.1016/j.jnutbio.2012.01.015.
[15]SANDER K,BEATRICE D,WALTER W.Peroxisome proliferatoractivated receptor a mediates the adaptive response to fasting[J].Journal of Clinical Investigation,1999,103(11):1489-1498.DOI:10.1172/JCI6223.
[16]MANDARD S,MULLER M,KERSTEN S.Peroxisome proliferatoractivated receptor alpha target genes[J].Cellular and Molecular Life Sciences,2004,61(4):393-416.DOI:10.1155/2010/612089.
[17]AHMED W,ZIOZENKOVA O,BROWN J,et al.PPARs and their metabolic modulation:new mechanisms for transcriptional regulation[J].International Medicine Journal,2007,262(2):184-198.DOI:10.1111/j.1365-2796.2007.01825.x.
[18]COSTET P,LEGENDRE C,MORE J,et al.Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis[J].Journal of Biological Chemistry,1998,273(45):29577-29585.DOI:10.1074/jbc.273.45.295.
[19]DELUCA J G,DOEBBER T W,KELLY L J,et al.Evidence for peroxisome proliferator-activated receptor(PPAR)alpha-independent peroxisome proliferation:effects of PPARgamma/delta-specific agonists in PPARalpha-null mice[J].Molecular Pharmacology,2000,58(3):470-476.
[20]BRUN R P,TONTONOZ P,FORMAN B M,et al.Differential activation of adipogenesis by multiple PPAR isoforms[J].Genes&Development,1996,10(8):974-984.DOI:10.1101/gad.10.8.974.
[21]WU Z,ROSEN E D,BRUN R,et al.Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity[J].Molcular Cell,1999,3(2):151-158.DOI:10.1016/S1097-2765(00)80306-8.
[22]SPIEGELMAN B M,FLIER J S.Adipogenesis and obesity:rounding out the big picture[J].Cell,1996,87(3):377-389.DOI:10.1016/S0092-8674(00)81359-8.
[23]MANDRUP S,LANE M D.Regulating adipogenesis[J].Journal of Biological Chemistry,1997,272(9):5367-5370.
[24]CHAWLA A,LAZAR M A.Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival[J].Proceedings of the National Academy of Sciences of the United States of America,1994,91(5):1786-1790.DOI:10.1073/pnas.91.5.1786.
[25]AILHAUD G.Molecular mechanisms of adipocyte differentiation[J].Journal of Endocrinology,1997,155(2):201-202.
[26]PARK K W,HALPERIN D S,TONTONOZ P.Before they were fat:adipocyte progenitors[J].Cell Metabolism.2008,8(6):454-457.DOI:10.1016/j.cmet.2008.11.001.
[27]SIERSBAEK R,NIELSEN R,MANDRUP S.PPARgamma in adipocyte differentiation and metabolism-novel insights from genome-wide studies[J].FEBS Letters,2010,584(15):3242-3249.DOI:10.1016/j.febslet.2010.06.010.
[28]ROSEN E D,HSU C H,WANG X,et al.C/EBPalpha induces adipogenesis through PPARgamma:a unified pathway[J].Genes&Development,2002,16(1):22-26.
[29]MATSUSUE K,PETERS J M,GONZALEZ F J.PPARβ/δpotentiates PPARy-stimulated adipocyte differentiation[J].Faseb Journal,2004,18(12):1477-1479.
[30]CHOI J H,BANKS A S,ESTALL JL,et al.Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5[J].Nature,2010,466:451-456.DOI:10.1038/nature09291.
[31]LI Pingping,FAN Wuqian,XU Jianfeng,et al.Adipocyte NCoR knockout decreases PPARy phosphorylation and enhances PPARy activity and insulin sensitivity[J].Cell,2011,147(4):815-826.DOI:10.1016/j.cell.2011.09.050.
[32]KAWAI M,ROSEN C J.PPARy:a circadian transcription factor in adipogenesis and osteogenesis[J].Nature Reviews Endocrinology,2010,6(11):629-636.DOI:10.1038/nrendo.2010.155.
[33]AHMED M,GAFFEN S L.IL-17 inhibits adipogenesis in part via C/EBPα,PPARγand Kruppel-like factors[J].Cytokine,2013,61(3):898-905.DOI:10.1016/j.cyto.2012.12.007.
[34]KIM S Y,KIM A Y,LEE H W,et al.miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression[J].Biochemical and Biophysical Research Communications,2010,392(3):323-328.DOI:10.1016/j.bbrc.2010.01.012.
[35]吴宗松.miR-27b通过靶向于PPARγ触发脂肪细胞分化[D].杨凌:西北农林科技大学,2009:40-41.
[36]MEERSON A,TRAURIG M,OSSOWSKI V,et al.Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-a[J].Diabetologia,2013,56(9):1971-1979.DOI:10.1007/s00125-013-2950-9.
[37]PARK H S,JU U I,PARK J W,et al.PPARy neddylation essential for adipogenesis is a potential target for treating obesity[J].Cell Death and Differentiation,2016,23(8):1296-1311.DOI:10.1038/cdd.2016.6.
[38]BURNS K A,VANDEN H J P.Modulation of PPAR activity via phosphorylation[J].Biochimica et Biophysica Acta-Biomembranes,2007,1771(8):952-960.
[39]YU Y H,CHANG Y C,SU T H,et al.Prostaglandin reductase-3negatively modulates adipogenesis through regulation of PPARy activity[J].Journal of Lipid Research,2013,54(9):2391-2399.DOI:10.1194/jlr.M037556.
[40]ZHENG W L,FENG X,QIU L,et al.Identification of the antibiotic ionomycin as an unexpected peroxisome proliferator-activated receptorγ(PPARγ)ligand with a unique binding mode and effective glucoselowering activity in a mouse model of diabetes[J].Diabetologia,2013,56(2):401-411.DOI:20.1007/s00125-012-2777-9.
[41]FENG L,LUO H,XU Z,et al.Bavachinin,as a novel natural panPPAR agonist,exhibits unique synergistic effects with synthetic PPAR-γand PPAR-αagonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice[J].Diabetologia,2016,59(6):1276-1286.DOI:10.1007/s00125-016-3912-9.
[42]毛磊,徐慧,田迎樱,等.叶瓜参长链碱抑制3T3-L1前脂肪细胞分化及其作用机制研究[J].食品科学,2015,36(23):241-246.DOI:10.7506/spkx1002-6630-201523044.
[43]王振华,邱理红,王占洋,等.异甘草素对3T3-L1前脂肪细胞分化的抑制作用[J].食品科学,2016,37(1):157-162.DOI:10.7506/spkx1002-6630-201601028.
[44]金凤,康凯夫,陈坚平.p53、MDM2、eyelin G在星形细胞瘤中的表达及与肿瘤分化和预后的关系[J].实用医学杂志,2007,23(11):1635-1637.
[45]GARCIA-ROJAS P,ANTARAMIAN A,GONZALEZ-DAVALOS L,et al.Induction of peroxisomal proliferator-activated receptor gamma and peroxisomal proliferator-activated receptor gamma coactivator1 by unsaturated fatty acids,retinoic acid,and carotenoids in preadipocytes obtained from bovine white adipose tissue[J].Journal of Animal Science,2010,88(5):1801-1808.DOI:10.2527/jas.2009-2579.
[46]TAXVIG C,DREISIG K,BOBERG J,et al.Differential effects of environmental chemicals and food contaminants on adipogenesis,biomarker release and PPARy activation[J].Molecular and Cellular Endocrinology,2012,361(1/2):106-115.DOI:10.1016/j.mce.2012.03.021.
[47]DIEZKO R,SUSKE G.Ligand binding reduces SUMOylation of the peroxisome proliferator-activated receptor y(PPARy)activation function 1(AF1)domain[J].PLoS ONE,2013,8(6):264-272.DOI:10.1371/journal.pone.0066947.
[48]TSUKAMOTO T,NAKATA R,TAMURA U,et al.Vaticanol C,a resveratrol tetramer,activates PPARαand PPARβ/δin vitro and in vivo[J].Nutrition&Metabolism,2010,7(1):1-8.DOI:10.1186/1743-7075-7-46.
[49]SONG M,TIAN X,LU M,et al.Genistein exerts growth inhibition on human osteosarcoma MG-63 cells via PPARγpathway[J].International Journal of Radiation Oncology Biology Physics,2015,46(3):1131-1140.DOI:10.3892/ijo.2015.2829.
[50]GOTO T,KIM Y I,FUNAKOSHI K,et al.Farnesol,an isoprenoid,improves metabolic abnormalities in mice via both PPARα-dependent and-independent pathways[J].American Journal of Physiology-endocrinology and Metabolism,2011,301(5):1022-1032.DOI:10.1152/ajpendo.00061.2011.
[51]SOUBH A A,AADALLAH D M,El-ABBAR H S.Geraniol ameliorates TNBS-induced colitis:involvement of Wnt/β-catenin,p38MAPK,NFkB,and PPARy signaling pathways[J].Life Science,2015,136:142-150.DOI:10.1016/j.lfs.2015.07.004.
[52]SHANG W,YANG Y,JIANG B,et al.Ginsenoside Rb1 promotes adipogenesis in 3T3-L1 cells by enhancing PPARgamma2 and C/EBPalpha gene expression[J].Life Science,2007,23,80(7):618-625.DOI:10.1016/j.lfs.2006.10.021.
[53]HAN K L,JUNG M H,SOHN J H,et al.Ginsenoside20S-protopanaxatriol(PPT)activates peroxisome proliferator-activated receptor gamma(PPARgamma)in 3T3-L1 adipocytes[J].Biological&Pharmaceutical Bulletin,2006,29(1):110-113.DOI:10.1248/bpb.29.110.
[54]YANG Y,SHANG W,ZHOU L,et al.Emodin with PPARgamma ligand-binding activity promotes adipocyte differentiation and increases glucose uptake in 3T3-L1 cells[J].Biochemical and Biophysical Research Communications,2007,353(2):225-230.DOI:10.1016/j.bbrc.2006.11.134.
[55]ZHOU Y,ZHENG S,LIN J,et al.The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in rat activated hepatic stellate cell in vitro[J].Laboratory Investigation,2007,87(5):488-498.DOI:10.1038/labinvest.3700532.
[56]GONG Z,HUANG C,SHENG X,et al.The role of tanshinoneⅡA in the treatment of obesity through PPARgamma antagonism[J].Endocrinology,2008,150(1):104-113.DOI:10.1210/en.2008-0322.
[57]HUANG C,ZHANG Y,GONG Z,et al.Berberine inhibits 3T3-L1adipocyte differentiation through the PPARgamma pathway[J].Biochemical and Biophysical Research Communications,2006,348(2):571-578.DOI:10.1016/j.bbrc.2006.07.095.
[58]刘毅,王文健,陈伟华,等.黄芪多糖对3T3-L1前脂肪细胞增殖和分化的影响[J].中西医结合杂志,2007,5(4):421-426.
[59]窦勤,魏媛媛,李郁,等.石榴花多酚对糖尿病大鼠IL-6、TXB2及PPAR-γmRNA基因表达的影响[J].中国药理学通报,2010,26(6):794-797.
[60]傅晓东,何燕铭,陈伟华,等.蒲黄总黄酮对3T3-L1前脂肪细胞增殖分化及相关基因表达的影响[J].医学研究生学报,2010,23(5):456-459.DOI:10.3969/j.issn.1008-8199.2010.05.003.
[2]GUAN Y.Targeting peroxisome proliferator-activated receptors(PPARs)in kidney and urologic disease[J].Minerva Urologica e Nefrologica,2002,54(2):65-79.
[3]CHINETTI G,FRUCHART J C,STAELS B.Peroxisome proliferatoractivated receptors(PPARs):nuclear receptors at the crossroads between lipid metabolism and inflammation[J].Inflammation Research,2000,49(10):497-505.
[4]REDDY J K.Peroxisome proliferators and peroxisome proliferatoractivated receptorα[J].The American Journal of Pathology,2004,164(6):2305-2321.
[5]KERSTEN S,DESVERGNE B,WAHLI W.Roles of PPARs in health and disease[J].Nature,2000,405:421-424.DOI:10.1038/35013000.
[6]MORAES L A,PIQUERAS L,BSSHOP-BAILEY D.Peroxisome proliferator-activated receptors and inflammation[J].Pharmacology&Therapeutics,2006,110(3):371-385.DOI:10.1016/j.pharmthera.2005.08.007.
[7]ISSEMANN I,GREEN S.Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators[J].Nature,1990,347:1155-1208.DOI:10.1038/347645a0.
[8]ABBOTT B D.Review of the expression of peroxisome proliferatoractivated receptors alpha(PPARα),beta(PPARβ),and gamma(PPARγ)in rodent and human development[J].Reproductive Toxicology,2009,27(3/4):246-257.DOI:10.1016/j.reprotox.2008.10.001.
[9]HSU M H,PALMER C N,SONG W,et al.A carboxyl terminal extension of the zinc finger domain contributes to the specificity and polarity of peroxisome proliferator-activated receptor DNA binding[J].Journal of Biological Chemistry,1998,273(43):27988-27997.DOI:10.1074/jbc.273.43.279.
[10]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,2010:54-55.
[11]王丽,那威,王宇祥,等.鸡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(4):454-464.DOI:10.3724/SP.J.1005.2012.00454.
[12]GUO L,SUN B,SHANG Z,et al.Comparison of adipose tissue cellularity in chicken lines divergently selected for fatness[J].Poultry Science,2011,90(9):2024-2034.DOI:10.3382/ps.2010-00863.
[13]PETROVIC N,WALDEN T B,SHALINA I G et al.Chronic peroxisome proliferator-activated receptor gamma(PPARgamma)activation of epididymally derived whiteadipocyte cultures reveals a population of thermogenically competent,UCP1-containing adipocytes molecularly distinct from classic brown adipocytes[J].Journal of Biological Chemistry,2010,285(10):7153-7164.DOI:10.1074/jbc.M109.053942.
[14]CHOI S H,CHUNG K Y,JOHNSON B J,et al.Co-culture of bovine muscle satellite cells with preadipocytes increases PPARγand C/EBPβgene expression in differentiated myoblasts and increases GPR43 gene expression in adipocytes[J].Journal of Nutritional Biochemistry,2013,24(3):539-543.DOI:10.1016/j.jnutbio.2012.01.015.
[15]SANDER K,BEATRICE D,WALTER W.Peroxisome proliferatoractivated receptor a mediates the adaptive response to fasting[J].Journal of Clinical Investigation,1999,103(11):1489-1498.DOI:10.1172/JCI6223.
[16]MANDARD S,MULLER M,KERSTEN S.Peroxisome proliferatoractivated receptor alpha target genes[J].Cellular and Molecular Life Sciences,2004,61(4):393-416.DOI:10.1155/2010/612089.
[17]AHMED W,ZIOZENKOVA O,BROWN J,et al.PPARs and their metabolic modulation:new mechanisms for transcriptional regulation[J].International Medicine Journal,2007,262(2):184-198.DOI:10.1111/j.1365-2796.2007.01825.x.
[18]COSTET P,LEGENDRE C,MORE J,et al.Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis[J].Journal of Biological Chemistry,1998,273(45):29577-29585.DOI:10.1074/jbc.273.45.295.
[19]DELUCA J G,DOEBBER T W,KELLY L J,et al.Evidence for peroxisome proliferator-activated receptor(PPAR)alpha-independent peroxisome proliferation:effects of PPARgamma/delta-specific agonists in PPARalpha-null mice[J].Molecular Pharmacology,2000,58(3):470-476.
[20]BRUN R P,TONTONOZ P,FORMAN B M,et al.Differential activation of adipogenesis by multiple PPAR isoforms[J].Genes&Development,1996,10(8):974-984.DOI:10.1101/gad.10.8.974.
[21]WU Z,ROSEN E D,BRUN R,et al.Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity[J].Molcular Cell,1999,3(2):151-158.DOI:10.1016/S1097-2765(00)80306-8.
[22]SPIEGELMAN B M,FLIER J S.Adipogenesis and obesity:rounding out the big picture[J].Cell,1996,87(3):377-389.DOI:10.1016/S0092-8674(00)81359-8.
[23]MANDRUP S,LANE M D.Regulating adipogenesis[J].Journal of Biological Chemistry,1997,272(9):5367-5370.
[24]CHAWLA A,LAZAR M A.Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival[J].Proceedings of the National Academy of Sciences of the United States of America,1994,91(5):1786-1790.DOI:10.1073/pnas.91.5.1786.
[25]AILHAUD G.Molecular mechanisms of adipocyte differentiation[J].Journal of Endocrinology,1997,155(2):201-202.
[26]PARK K W,HALPERIN D S,TONTONOZ P.Before they were fat:adipocyte progenitors[J].Cell Metabolism.2008,8(6):454-457.DOI:10.1016/j.cmet.2008.11.001.
[27]SIERSBAEK R,NIELSEN R,MANDRUP S.PPARgamma in adipocyte differentiation and metabolism-novel insights from genome-wide studies[J].FEBS Letters,2010,584(15):3242-3249.DOI:10.1016/j.febslet.2010.06.010.
[28]ROSEN E D,HSU C H,WANG X,et al.C/EBPalpha induces adipogenesis through PPARgamma:a unified pathway[J].Genes&Development,2002,16(1):22-26.
[29]MATSUSUE K,PETERS J M,GONZALEZ F J.PPARβ/δpotentiates PPARy-stimulated adipocyte differentiation[J].Faseb Journal,2004,18(12):1477-1479.
[30]CHOI J H,BANKS A S,ESTALL JL,et al.Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5[J].Nature,2010,466:451-456.DOI:10.1038/nature09291.
[31]LI Pingping,FAN Wuqian,XU Jianfeng,et al.Adipocyte NCoR knockout decreases PPARy phosphorylation and enhances PPARy activity and insulin sensitivity[J].Cell,2011,147(4):815-826.DOI:10.1016/j.cell.2011.09.050.
[32]KAWAI M,ROSEN C J.PPARy:a circadian transcription factor in adipogenesis and osteogenesis[J].Nature Reviews Endocrinology,2010,6(11):629-636.DOI:10.1038/nrendo.2010.155.
[33]AHMED M,GAFFEN S L.IL-17 inhibits adipogenesis in part via C/EBPα,PPARγand Kruppel-like factors[J].Cytokine,2013,61(3):898-905.DOI:10.1016/j.cyto.2012.12.007.
[34]KIM S Y,KIM A Y,LEE H W,et al.miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression[J].Biochemical and Biophysical Research Communications,2010,392(3):323-328.DOI:10.1016/j.bbrc.2010.01.012.
[35]吴宗松.miR-27b通过靶向于PPARγ触发脂肪细胞分化[D].杨凌:西北农林科技大学,2009:40-41.
[36]MEERSON A,TRAURIG M,OSSOWSKI V,et al.Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-a[J].Diabetologia,2013,56(9):1971-1979.DOI:10.1007/s00125-013-2950-9.
[37]PARK H S,JU U I,PARK J W,et al.PPARy neddylation essential for adipogenesis is a potential target for treating obesity[J].Cell Death and Differentiation,2016,23(8):1296-1311.DOI:10.1038/cdd.2016.6.
[38]BURNS K A,VANDEN H J P.Modulation of PPAR activity via phosphorylation[J].Biochimica et Biophysica Acta-Biomembranes,2007,1771(8):952-960.
[39]YU Y H,CHANG Y C,SU T H,et al.Prostaglandin reductase-3negatively modulates adipogenesis through regulation of PPARy activity[J].Journal of Lipid Research,2013,54(9):2391-2399.DOI:10.1194/jlr.M037556.
[40]ZHENG W L,FENG X,QIU L,et al.Identification of the antibiotic ionomycin as an unexpected peroxisome proliferator-activated receptorγ(PPARγ)ligand with a unique binding mode and effective glucoselowering activity in a mouse model of diabetes[J].Diabetologia,2013,56(2):401-411.DOI:20.1007/s00125-012-2777-9.
[41]FENG L,LUO H,XU Z,et al.Bavachinin,as a novel natural panPPAR agonist,exhibits unique synergistic effects with synthetic PPAR-γand PPAR-αagonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice[J].Diabetologia,2016,59(6):1276-1286.DOI:10.1007/s00125-016-3912-9.
[42]毛磊,徐慧,田迎樱,等.叶瓜参长链碱抑制3T3-L1前脂肪细胞分化及其作用机制研究[J].食品科学,2015,36(23):241-246.DOI:10.7506/spkx1002-6630-201523044.
[43]王振华,邱理红,王占洋,等.异甘草素对3T3-L1前脂肪细胞分化的抑制作用[J].食品科学,2016,37(1):157-162.DOI:10.7506/spkx1002-6630-201601028.
[44]金凤,康凯夫,陈坚平.p53、MDM2、eyelin G在星形细胞瘤中的表达及与肿瘤分化和预后的关系[J].实用医学杂志,2007,23(11):1635-1637.
[45]GARCIA-ROJAS P,ANTARAMIAN A,GONZALEZ-DAVALOS L,et al.Induction of peroxisomal proliferator-activated receptor gamma and peroxisomal proliferator-activated receptor gamma coactivator1 by unsaturated fatty acids,retinoic acid,and carotenoids in preadipocytes obtained from bovine white adipose tissue[J].Journal of Animal Science,2010,88(5):1801-1808.DOI:10.2527/jas.2009-2579.
[46]TAXVIG C,DREISIG K,BOBERG J,et al.Differential effects of environmental chemicals and food contaminants on adipogenesis,biomarker release and PPARy activation[J].Molecular and Cellular Endocrinology,2012,361(1/2):106-115.DOI:10.1016/j.mce.2012.03.021.
[47]DIEZKO R,SUSKE G.Ligand binding reduces SUMOylation of the peroxisome proliferator-activated receptor y(PPARy)activation function 1(AF1)domain[J].PLoS ONE,2013,8(6):264-272.DOI:10.1371/journal.pone.0066947.
[48]TSUKAMOTO T,NAKATA R,TAMURA U,et al.Vaticanol C,a resveratrol tetramer,activates PPARαand PPARβ/δin vitro and in vivo[J].Nutrition&Metabolism,2010,7(1):1-8.DOI:10.1186/1743-7075-7-46.
[49]SONG M,TIAN X,LU M,et al.Genistein exerts growth inhibition on human osteosarcoma MG-63 cells via PPARγpathway[J].International Journal of Radiation Oncology Biology Physics,2015,46(3):1131-1140.DOI:10.3892/ijo.2015.2829.
[50]GOTO T,KIM Y I,FUNAKOSHI K,et al.Farnesol,an isoprenoid,improves metabolic abnormalities in mice via both PPARα-dependent and-independent pathways[J].American Journal of Physiology-endocrinology and Metabolism,2011,301(5):1022-1032.DOI:10.1152/ajpendo.00061.2011.
[51]SOUBH A A,AADALLAH D M,El-ABBAR H S.Geraniol ameliorates TNBS-induced colitis:involvement of Wnt/β-catenin,p38MAPK,NFkB,and PPARy signaling pathways[J].Life Science,2015,136:142-150.DOI:10.1016/j.lfs.2015.07.004.
[52]SHANG W,YANG Y,JIANG B,et al.Ginsenoside Rb1 promotes adipogenesis in 3T3-L1 cells by enhancing PPARgamma2 and C/EBPalpha gene expression[J].Life Science,2007,23,80(7):618-625.DOI:10.1016/j.lfs.2006.10.021.
[53]HAN K L,JUNG M H,SOHN J H,et al.Ginsenoside20S-protopanaxatriol(PPT)activates peroxisome proliferator-activated receptor gamma(PPARgamma)in 3T3-L1 adipocytes[J].Biological&Pharmaceutical Bulletin,2006,29(1):110-113.DOI:10.1248/bpb.29.110.
[54]YANG Y,SHANG W,ZHOU L,et al.Emodin with PPARgamma ligand-binding activity promotes adipocyte differentiation and increases glucose uptake in 3T3-L1 cells[J].Biochemical and Biophysical Research Communications,2007,353(2):225-230.DOI:10.1016/j.bbrc.2006.11.134.
[55]ZHOU Y,ZHENG S,LIN J,et al.The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARgamma in rat activated hepatic stellate cell in vitro[J].Laboratory Investigation,2007,87(5):488-498.DOI:10.1038/labinvest.3700532.
[56]GONG Z,HUANG C,SHENG X,et al.The role of tanshinoneⅡA in the treatment of obesity through PPARgamma antagonism[J].Endocrinology,2008,150(1):104-113.DOI:10.1210/en.2008-0322.
[57]HUANG C,ZHANG Y,GONG Z,et al.Berberine inhibits 3T3-L1adipocyte differentiation through the PPARgamma pathway[J].Biochemical and Biophysical Research Communications,2006,348(2):571-578.DOI:10.1016/j.bbrc.2006.07.095.
[58]刘毅,王文健,陈伟华,等.黄芪多糖对3T3-L1前脂肪细胞增殖和分化的影响[J].中西医结合杂志,2007,5(4):421-426.
[59]窦勤,魏媛媛,李郁,等.石榴花多酚对糖尿病大鼠IL-6、TXB2及PPAR-γmRNA基因表达的影响[J].中国药理学通报,2010,26(6):794-797.
[60]傅晓东,何燕铭,陈伟华,等.蒲黄总黄酮对3T3-L1前脂肪细胞增殖分化及相关基因表达的影响[J].医学研究生学报,2010,23(5):456-459.DOI:10.3969/j.issn.1008-8199.2010.05.003.