Shp2 Controls Female Body Weight and Energy Balance by Integrating Leptin and Estrogen Signals

	Shp2 Controls Female Body Weight and Energy Balance by Integrating Leptin and Estrogen Signals
	He, Z; Zhang, SS; Meng, QY; Li, SW; Zhu, HH; Raquil, MA; Alderson, N; Zhang, H; Wu, JR; Rui, LY
刊名	MOLECULAR AND CELLULAR BIOLOGY
	2012
卷号	32 期号:10 页码:1867-1878
通讯作者	Feng, GS (reprint author), Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.,dongsheng.cai@einstein.yu.edu ; gfeng@ucsd.edu
英文摘要	In mammals, leptin regulates food intake and energy balance mainly through the activation of LepRb in the hypothalamus, and estrogen has a leptin-like effect in the hypothalamic control of metabolism. However, it remains to be elucidated how estrogen signaling is intertwined with the leptin pathway. We show here that Shp2, a nonreceptor tyrosine phosphatase, acts to integrate leptin and estrogen signals. The expression of a dominant-active mutant (Shp2(D61A)) in forebrain neurons conferred female, but not male, transgenic mice resistance to high-fat diet (HFD)-induced obesity and liver steatosis, accompanied by improved insulin sensitivity and glucose homeostasis. Fed with either HFD or regular chow food, Shp2(D61A) female mice showed dramatically enhanced leptin sensitivity. Microinjection of Shp2(D61A)-expressing adeno-associated virus into mediobasal hypothalamus elicited a similar antiobese effect in female mice. Biochemical analyses showed a physical association of Shp2 with estrogen receptor alpha, which is necessary for the synergistic and persistent activation of Erk by leptin and estrogen. Together, these results elucidate a mechanism for the direct cross talk of leptin and estrogen signaling and offer one explanation for the propensity of postmenopausal women to develop obesity.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	TYROSINE-PHOSPHATASE ; METABOLIC SYNDROME ; MICE ; OBESITY ; RECEPTOR ; CANCER ; EXPRESSION ; HYPOTHALAMUS ; METAANALYSIS ; HOMEOSTASIS
收录类别	SCI
语种	英语
WOS记录号	WOS:000303840100009
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/652]
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	He, Z,Zhang, SS,Meng, QY,et al. Shp2 Controls Female Body Weight and Energy Balance by Integrating Leptin and Estrogen Signals[J]. MOLECULAR AND CELLULAR BIOLOGY,2012,32(10):1867-1878.
APA	He, Z.,Zhang, SS.,Meng, QY.,Li, SW.,Zhu, HH.,...&Feng, GS.(2012).Shp2 Controls Female Body Weight and Energy Balance by Integrating Leptin and Estrogen Signals.MOLECULAR AND CELLULAR BIOLOGY,32(10),1867-1878.
MLA	He, Z,et al."Shp2 Controls Female Body Weight and Energy Balance by Integrating Leptin and Estrogen Signals".MOLECULAR AND CELLULAR BIOLOGY 32.10(2012):1867-1878.