beta-Arrestin-1 Protein Represses Adipogenesis and Inflammatory Responses through Its Interaction with Peroxisome Proliferator-activated Receptor-gamma (PPAR gamma)

	beta-Arrestin-1 Protein Represses Adipogenesis and Inflammatory Responses through Its Interaction with Peroxisome Proliferator-activated Receptor-gamma (PPAR gamma)
	Zhuang, LN; Hu, WX; Xin, SM; Zhao, J; Pei, G
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2011
卷号	286 期号:32 页码:28403-28413
通讯作者	Zhao, J (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,jzhao@sibs.ac.cn ; gpei@sibs.ac.cn
英文摘要	One of the master regulators of adipogenesis and macrophage function is peroxisome proliferator-activated receptor-gamma (PPAR gamma). Here, we report that a deficiency of beta-arrestin-1 expression affects PPAR gamma-mediated expression of lipid metabolic genes and inflammatory genes. Further mechanistic studies revealed that beta-arrestin-1 interacts with PPAR gamma. beta-Arrestin-1 suppressed the formation of a complex between PPAR gamma and 9-cis-retinoic acid receptor-alpha through its direct interaction with PPAR gamma. The interaction of beta-arrestin-1 with PPAR gamma repressed PPAR gamma/9-cis-retinoic acid receptor-alpha function but promoted PPAR gamma/nuclear receptor corepressor function in PPAR gamma-mediated adipogenesis and inflammatory gene expression. Consistent with these results, a deficiency of beta-arrestin-1 binding to PPAR gamma abolished its suppression of PPAR gamma-dependent adipogenesis and inflammatory responses. These results indicate that the regulation of PPAR gamma by beta-arrestin-1 is critical. Furthermore, in vivo expression of beta-arrestin-1 (but not the binding-deficient mutant) significantly repressed adipogenesis, macrophage infiltration, and diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Therefore, our findings not only reveal a molecular mechanism for the modulation of obesity by beta-arrestin-1 but also suggest a potential tactical approach against obesity and its associated metabolic disorders.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	PANCREATIC BETA-CELLS ; INSULIN-RESISTANCE ; TRANSCRIPTION ; COMPLEX ; DIFFERENTIATION ; ARRESTIN ; OBESITY ; FAT ; FIBROBLASTS ; BEHAVIOR
收录类别	SCI
语种	英语
WOS记录号	WOS:000293557800056
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/889]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhuang, LN,Hu, WX,Xin, SM,et al. beta-Arrestin-1 Protein Represses Adipogenesis and Inflammatory Responses through Its Interaction with Peroxisome Proliferator-activated Receptor-gamma (PPAR gamma)[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(32):28403-28413.
APA	Zhuang, LN,Hu, WX,Xin, SM,Zhao, J,&Pei, G.(2011).beta-Arrestin-1 Protein Represses Adipogenesis and Inflammatory Responses through Its Interaction with Peroxisome Proliferator-activated Receptor-gamma (PPAR gamma).JOURNAL OF BIOLOGICAL CHEMISTRY,286(32),28403-28413.
MLA	Zhuang, LN,et al."beta-Arrestin-1 Protein Represses Adipogenesis and Inflammatory Responses through Its Interaction with Peroxisome Proliferator-activated Receptor-gamma (PPAR gamma)".JOURNAL OF BIOLOGICAL CHEMISTRY 286.32(2011):28403-28413.