Leptin and Insulin Act on POMC Neurons to Promote the Browning of White Fat

被引：324

作者：

Dodd, Garron T. ^{[1
]}

Decherf, Stephanie ^{[1
]}

Loh, Kim ^{[1
]}

Simonds, Stephanie E. ^{[2
]}

Wiede, Florian ^{[1
]}

Balland, Eglantine ^{[2
]}

Merry, Troy L. ^{[1
]}

Muenzberg, Heike ^{[3
]}

Zhang, Zhong-Yin ^{[4
]}

Kahn, Barbara B. ^{[5
,6
]}

Neel, Benjamin G. ^{[7
,8
]}

Bence, Kendra K. ^{[9
]}

Andrews, Zane B. ^{[2
]}

Cowley, Michael A. ^{[2
]}

Tiganis, Tony ^{[1
]}

机构：

[1] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[2] Monash Univ, Dept Physiol, Clayton, Vic 3800, Australia

[3] LSU Syst, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA

[4] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[5] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Med, Boston, MA 02215 USA

[6] Harvard Univ, Sch Med, Boston, MA 02215 USA

[7] Univ Toronto, Campbell Family Canc Res Inst, Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada

[8] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada

[9] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA

来源：

CELL | 2015年 / 160卷 / 1-2期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

DIET-INDUCED OBESITY; ARCUATE PROOPIOMELANOCORTIN NEURONS; ADIPOSE-TISSUE; GLUCOSE-HOMEOSTASIS; ENERGY-BALANCE; TRPC CHANNELS; AGRP NEURONS; BODY-WEIGHT; ACTIVATION; RESISTANCE;

D O I：

10.1016/j.cell.2014.12.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The primary task of white adipose tissue (WAT) is the storage of lipids. However, "beige'' adipocytes also exist in WAT. Beige adipocytes burn fat and dissipate the energy as heat, but their abundance is diminished in obesity. Stimulating beige adipocyte development, or WAT browning, increases energy expenditure and holds potential for combating metabolic disease and obesity. Here, we report that insulin and leptin act together on hypothalamic neurons to promote WAT browning and weight loss. Deletion of the phosphatases PTP1B and TCPTP enhanced insulin and leptin signaling in proopiomelanocortin neurons and prevented diet-induced obesity by increasing WAT browning and energy expenditure. The coinfusion of insulin plus leptin into the CNS or the activation of proopiomelanocortin neurons also increased WAT browning and decreased adiposity. Our findings identify a homeostatic mechanism for coordinating the status of energy stores, as relayed by insulin and leptin, with the central control of WAT browning.

引用

页码：88 / 104

页数：17

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