CRTC3 Links Catecholamine Signalling to Energy Balance

Overview

Journal Nature

Specialty Science

Date 2010 Dec 18

PMID 21164481

Citations 81

Authors

Youngsup Song

Judith Altarejos

Mark O Goodarzi

Hiroshi Inoue

Xiuqing Guo

Rebecca Berdeaux

Jeong-Ho Kim

Jason Goode

Motoyuki Igata

Jose C Paz

Meghan F Hogan

Pankaj K Singh

Naomi Goebel

Lili Vera

Nina Miller

Jinrui Cui

Michelle R Jones

Yii-Der I Chen

Kent D Taylor

Willa A Hsueh

Jerome I Rotter

Marc Montminy

Affiliations

Soon will be listed here.

Abstract

The adipose-derived hormone leptin maintains energy balance in part through central nervous system-mediated increases in sympathetic outflow that enhance fat burning. Triggering of β-adrenergic receptors in adipocytes stimulates energy expenditure by cyclic AMP (cAMP)-dependent increases in lipolysis and fatty-acid oxidation. Although the mechanism is unclear, catecholamine signalling is thought to be disrupted in obesity, leading to the development of insulin resistance. Here we show that the cAMP response element binding (CREB) coactivator Crtc3 promotes obesity by attenuating β-adrenergic receptor signalling in adipose tissue. Crtc3 was activated in response to catecholamine signals, when it reduced adenyl cyclase activity by upregulating the expression of Rgs2, a GTPase-activating protein that also inhibits adenyl cyclase activity. As a common human CRTC3 variant with increased transcriptional activity is associated with adiposity in two distinct Mexican-American cohorts, these results suggest that adipocyte CRTC3 may play a role in the development of obesity in humans.

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