CRTC3 links catecholamine signalling to energy balance

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. HsuehJerome I. Rotter, Marc Montminy

Research output: Contribution to journalArticle

87 Citations (Scopus)

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 Î 2-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 Î 2-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.

Original languageEnglish (US)
Pages (from-to)933-939
Number of pages7
JournalNature
Volume468
Issue number7326
DOIs
StatePublished - Dec 16 2010

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Catecholamines
Obesity
Adenylyl Cyclases
Adipocytes
Cyclic AMP
Adrenergic Receptors
GTPase-Activating Proteins
Lipolysis
Adiposity
Response Elements
Leptin
Energy Metabolism
Insulin Resistance
Adipose Tissue
Fatty Acids
Central Nervous System
Fats
Hormones

ASJC Scopus subject areas

  • General

Cite this

Song, Y., Altarejos, J., Goodarzi, M. O., Inoue, H., Guo, X., Berdeaux, R., ... Montminy, M. (2010). CRTC3 links catecholamine signalling to energy balance. Nature, 468(7326), 933-939. https://doi.org/10.1038/nature09564

CRTC3 links catecholamine signalling to energy balance. / Song, Youngsup; Altarejos, Judith; Goodarzi, Mark O.; Inoue, Hiroshi; Guo, Xiuqing; Berdeaux, Rebecca; Kim, Jeong Ho; Goode, Jason; Igata, Motoyuki; Paz, Jose C.; Hogan, Meghan F.; Singh, Pankaj K.; Goebel, Naomi; Vera, Lili; Miller, Nina; Cui, Jinrui; Jones, Michelle R.; Chen, Yii Der I.; Taylor, Kent D.; Hsueh, Willa A.; Rotter, Jerome I.; Montminy, Marc.

In: Nature, Vol. 468, No. 7326, 16.12.2010, p. 933-939.

Research output: Contribution to journalArticle

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, Chen, YDI, Taylor, KD, Hsueh, WA, Rotter, JI & Montminy, M 2010, 'CRTC3 links catecholamine signalling to energy balance', Nature, vol. 468, no. 7326, pp. 933-939. https://doi.org/10.1038/nature09564
Song Y, Altarejos J, Goodarzi MO, Inoue H, Guo X, Berdeaux R et al. CRTC3 links catecholamine signalling to energy balance. Nature. 2010 Dec 16;468(7326):933-939. https://doi.org/10.1038/nature09564
Song, Youngsup ; Altarejos, Judith ; Goodarzi, Mark O. ; Inoue, Hiroshi ; Guo, Xiuqing ; Berdeaux, Rebecca ; Kim, Jeong Ho ; Goode, Jason ; Igata, Motoyuki ; Paz, Jose C. ; Hogan, Meghan F. ; Singh, Pankaj K. ; Goebel, Naomi ; Vera, Lili ; Miller, Nina ; Cui, Jinrui ; Jones, Michelle R. ; Chen, Yii Der I. ; Taylor, Kent D. ; Hsueh, Willa A. ; Rotter, Jerome I. ; Montminy, Marc. / CRTC3 links catecholamine signalling to energy balance. In: Nature. 2010 ; Vol. 468, No. 7326. pp. 933-939.
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