17β-Estradiol inhibition of PPARY-induced adipogenesis and adipocyte-specific gene expression  

作　　者：Sunhyo JEONG Michung YOON 

机构地区：[1]Department of Life Sciences, Mokwon University, Daejeon 302-729, Korea

出　　处：《Acta Pharmacologica Sinica》2011年第2期230-238,共9页中国药理学报（英文版）

摘　　要：Aim： To investigate the molecular interaction of peroxisome proliferator-activated receptor y （PPARy） with 17β-estradiol （E） in the regulation of adipogenesis. Methods： Female ovariectomized （OVX） mice and differentiated 3T3-L1 adipocytes were treated with combinations of the PPARy agonist troglitazone or E, and the variables and determinants of adipogenesis were measured using in vivo and in vitro approaches. Results： Troglitazone （250 mg.kg·d-1 for 13 weeks） decreased the size of adipocytes without the change in white adipose tissue （WAT） mass and increased the expression of adipocyte-specific genes, such as PPARy, adipocyte fatty acid binding protein, and lipoprotein lipase, compared with OVX control mice. E （0.05 mg/pellet, sc implanted） significantly reduced WAT mass, adipocyte size, and adipose marker gene expression. When mice were concomitantly treated with troglitazone and E, E blunted the effects of troglitazone on WAT mass, adipocyte size, and adipose PPARy target gene expression. Consistent with the in vivo data, E （10 μmol/L） treatment inhibited lipid accumulation and the expression of adipocyte-specific genes caused by troglitazone （10μmol/L） in 3T3-L1 cells. E （10μmol/L） also decreased troglitazone-induced PPARy reporter activity through both estrogen receptor （ER） α and ERβ. Mechanistic studies indicated that E （0.1μmol/L） decreased the DNA binding of PPARy induced by troglitazone （1μmol/L） and inhibited the recruitment of the PPARy coactivator CREB-binding protein. Conclusion： These results suggest that in vivo and in vitro treatment of E interferes with the actions of PPARy on adipogenesis by downregulating adipogenesis-related genes, which are mediated through the inhibition of PPARy coactivator recruitment. In addition, it is likely that the activities of PPARy activators may be enhanced in estrogen-deficient states.Aim： To investigate the molecular interaction of peroxisome proliferator-activated receptor y （PPARy） with 17β-estradiol （E） in the regulation of adipogenesis. Methods： Female ovariectomized （OVX） mice and differentiated 3T3-L1 adipocytes were treated with combinations of the PPARy agonist troglitazone or E, and the variables and determinants of adipogenesis were measured using in vivo and in vitro approaches. Results： Troglitazone （250 mg.kg·d-1 for 13 weeks） decreased the size of adipocytes without the change in white adipose tissue （WAT） mass and increased the expression of adipocyte-specific genes, such as PPARy, adipocyte fatty acid binding protein, and lipoprotein lipase, compared with OVX control mice. E （0.05 mg/pellet, sc implanted） significantly reduced WAT mass, adipocyte size, and adipose marker gene expression. When mice were concomitantly treated with troglitazone and E, E blunted the effects of troglitazone on WAT mass, adipocyte size, and adipose PPARy target gene expression. Consistent with the in vivo data, E （10 μmol/L） treatment inhibited lipid accumulation and the expression of adipocyte-specific genes caused by troglitazone （10μmol/L） in 3T3-L1 cells. E （10μmol/L） also decreased troglitazone-induced PPARy reporter activity through both estrogen receptor （ER） α and ERβ. Mechanistic studies indicated that E （0.1μmol/L） decreased the DNA binding of PPARy induced by troglitazone （1μmol/L） and inhibited the recruitment of the PPARy coactivator CREB-binding protein. Conclusion： These results suggest that in vivo and in vitro treatment of E interferes with the actions of PPARy on adipogenesis by downregulating adipogenesis-related genes, which are mediated through the inhibition of PPARy coactivator recruitment. In addition, it is likely that the activities of PPARy activators may be enhanced in estrogen-deficient states.

关 键 词：PPARY ADIPOGENESIS 17Β-ESTRADIOL TROGLITAZONE coactivator recruitment ovariectomized mice 3T3-L1 cells 

分 类 号：R[医药卫生]