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CRTC3 links catecholamine signalling to energy balance.

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.

Pubmed ID: 21164481

Authors

  • Song Y
  • Altarejos J
  • Goodarzi MO
  • Inoue H
  • Guo X
  • Berdeaux R
  • Kim JH
  • Goode J
  • Igata M
  • Paz JC
  • Hogan MF
  • Singh PK
  • Goebel N
  • Vera L
  • Miller N
  • Cui J
  • Jones MR
  • CHARGE Consortium
  • GIANT Consortium
  • Chen YD
  • Taylor KD
  • Hsueh WA
  • Rotter JI
  • Montminy M

Journal

Nature

Publication Data

December 16, 2010

Associated Grants

  • Agency: NCRR NIH HHS, Id: M01 RR000425-36
  • Agency: NCRR NIH HHS, Id: M01-RR00425
  • Agency: NHLBI NIH HHS, Id: N01 HC095159
  • Agency: NHLBI NIH HHS, Id: N01-HC95159
  • Agency: NHLBI NIH HHS, Id: N02 HL64278
  • Agency: NHLBI NIH HHS, Id: N02-HL64278
  • Agency: NIDDK NIH HHS, Id: P30 DK063491
  • Agency: NIDDK NIH HHS, Id: P30 DK063491-09
  • Agency: NIDDK NIH HHS, Id: P30-DK063491
  • Agency: NIDDK NIH HHS, Id: R01 DK033651
  • Agency: NIDDK NIH HHS, Id: R01 DK049777
  • Agency: NIDDK NIH HHS, Id: R01 DK049777-18
  • Agency: NIDDK NIH HHS, Id: R01 DK079888
  • Agency: NIDDK NIH HHS, Id: R01 DK079888-05
  • Agency: NHLBI NIH HHS, Id: R01 HL071205
  • Agency: NHLBI NIH HHS, Id: R01 HL071205-05
  • Agency: NHLBI NIH HHS, Id: R01 HL088457
  • Agency: NHLBI NIH HHS, Id: R01 HL088457-04
  • Agency: NIDDK NIH HHS, Id: R01-DK049777
  • Agency: NIDDK NIH HHS, Id: R01-DK083834
  • Agency: NIDDK NIH HHS, Id: R01-DK79888
  • Agency: NHLBI NIH HHS, Id: R01-HL088457
  • Agency: PHS HHS, Id: R01-L071205
  • Agency: NIDDK NIH HHS, Id: R37 DK083834
  • Agency: NIDDK NIH HHS, Id: R37 DK083834-26
  • Agency: NIDDK NIH HHS, Id: R37 DK083834-27

Mesh Terms

  • Adipocytes
  • Adipose Tissue
  • Animals
  • Body Temperature
  • Catecholamines
  • Cells, Cultured
  • Cyclic AMP
  • Cyclic AMP Response Element-Binding Protein
  • Dietary Fats
  • Energy Metabolism
  • Female
  • Genome-Wide Association Study
  • Humans
  • Insulin Resistance
  • Mexican Americans
  • Mice
  • Obesity
  • Phosphorylation
  • RGS Proteins
  • Receptors, Adrenergic, beta
  • Signal Transduction
  • Transcription Factors