Jong-Woo Sohn

The University of Texas Southwestern Medical Center

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Joel K. Elmquist

The University of Texas Southwestern Medical Center

Yong Xu

Children's Nutrition Research Center at Baylor College of Medicine

Kevin W. Williams

The University of Texas Southwestern Medical Center

Charlotte E. Lee

University of Stirling

Mi Hwa Kim

Korea University of Technology and Education

Laurent Gautron

The University of Texas Southwestern Medical Center

Kevin Wickman

University of Minnesota

Makoto Fukuda

Baylor College of Medicine

Ki Woo Kim

Yonsei University

Cláudia R. Vianna

The University of Texas Southwestern Medical Center

Cooperative Institutions

The University of Texas Southwestern Medical Center

Southwestern Medical Center

Beth Israel Deaconess Medical Center

Harvard University

Harvard University Press

Howard Hughes Medical Institute

Vanderbilt University

Baylor College of Medicine

Children's Nutrition Research Center at Baylor College of Medicine

Massachusetts General Hospital

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Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

Journal of Clinical Investigation (2013)

Eric D. Berglund Chen Liu Jong-Woo Sohn Tiemin Liu Mi Hwa Kim

Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.

Energy homeostasis

Hyperinsulinemia

Homeostasis

10.1172/jci70338

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Citations (207)

PI3K Signaling in the Ventromedial Hypothalamic Nucleus Is Required for Normal Energy Homeostasis

Cell Metabolism (2010)

Yong Xu Jennifer W. Hill Makoto Fukuda Laurent Gautron Jong-Woo Sohn

Energy homeostasis

Homeostasis

10.1016/j.cmet.2010.05.002