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

90 Scopus citations

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

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'CRTC3 links catecholamine signalling to energy balance'. Together they form a unique fingerprint.

  • Cite this

    Song, Y., Altarejos, J., Goodarzi, M. O., Inoue, H., Guo, X., Berdeaux, R., Kim, J. H., Goode, J., Igata, M., Paz, J. C., Hogan, M. F., Singh, P. K., Goebel, N., Vera, L., Miller, N., Cui, J., Jones, M. R., Chen, Y. D. I., Taylor, K. D., ... Montminy, M. (2010). CRTC3 links catecholamine signalling to energy balance. Nature, 468(7326), 933-939. https://doi.org/10.1038/nature09564