Ablation of gp78 in Liver Improves Hyperlipidemia and Insulin Resistance by Inhibiting SREBP to Decrease Lipid Biosynthesis

	Ablation of gp78 in Liver Improves Hyperlipidemia and Insulin Resistance by Inhibiting SREBP to Decrease Lipid Biosynthesis
	Liu, TF; Tang, JJ; Li, PS; Shen, Y; Li, JG; Miao, HH; Li, BL; Song, BL
刊名	CELL METABOLISM
	2012
卷号	16 期号:2 页码:213-225
通讯作者	Li, BL (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,blli@sibs.ac.cn ; blsong@sibs.ac.cn
英文摘要	gp78 is a membrane-anchored ubiquitin ligase mediating the degradation of HMG-CoA reductase (HMGCR) and Insig-1. As a rate-limiting enzyme in cholesterol biosynthesis, HMGCR undergoes rapid sterol-promoted degradation. In contrast, destruction of Insig-1 releases its inhibition on SREBP and stimulates the expression of lipogenic genes. Thus, gp78 has opposite effects on lipid biosynthesis. We here generated liver-specific gp78 knockout (L-gp78(-/-)) mice and showed that although the degradation of HMGCR was blunted, SREBP was suppressed due to the elevation of Insig-1/-2, and therefore the lipid biosynthesis was decreased. The L-gp78(-/-) mice were protected from diet-/age-induced obesity and glucose intolerance. The livers of L-gp78(-/-) mice produced more FGF21, which activated thermogenesis in brown adipocytes and enhanced energy expenditure. Together, the major function of gp78 in liver is regulating lipid biosynthesis through SREBP pathway. Ablation of gp78 decreases the lipid levels and increases FGF21, and is beneficial to patients with metabolic diseases.
学科主题	Cell Biology; Endocrinology & Metabolism
类目[WOS]	Cell Biology ; Endocrinology & Metabolism
关键词[WOS]	HMG-COA REDUCTASE ; STEROL-REGULATED UBIQUITINATION ; FATTY-ACID SYNTHESIS ; CHOLESTEROL-SYNTHESIS ; PPAR-ALPHA ; FEEDBACK-REGULATION ; ENERGY-EXPENDITURE ; ADIPOSE-TISSUE ; BROWN-FAT ; DEGRADATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000307615300011
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/541]
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	Liu, TF,Tang, JJ,Li, PS,et al. Ablation of gp78 in Liver Improves Hyperlipidemia and Insulin Resistance by Inhibiting SREBP to Decrease Lipid Biosynthesis[J]. CELL METABOLISM,2012,16(2):213-225.
APA	Liu, TF.,Tang, JJ.,Li, PS.,Shen, Y.,Li, JG.,...&Song, BL.(2012).Ablation of gp78 in Liver Improves Hyperlipidemia and Insulin Resistance by Inhibiting SREBP to Decrease Lipid Biosynthesis.CELL METABOLISM,16(2),213-225.
MLA	Liu, TF,et al."Ablation of gp78 in Liver Improves Hyperlipidemia and Insulin Resistance by Inhibiting SREBP to Decrease Lipid Biosynthesis".CELL METABOLISM 16.2(2012):213-225.