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

Eric D. Berglund, Chen Liu, Jong Woo Sohn, Tiemin Liu, Mi Hwa Kim, Charlotte E. Lee, Claudia R. Vianna, Kevin W. Williams, Yong Xu, Joel K. Elmquist

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5061-5070
Number of pages10
JournalJournal of Clinical Investigation
Volume123
Issue number12
DOIs
StatePublished - Dec 2 2013

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Receptor, Serotonin, 5-HT2C
Pro-Opiomelanocortin
Homeostasis
Neurons
Glucose
Serotonin Receptor Agonists
Obesity
Serotonin Agents
Ideal Body Weight
Appetite Depressants
Hyperphagia
Hyperinsulinism
High Fat Diet
Appetite
Tamoxifen
Hyperglycemia
Insulin Resistance
Weight Loss
Serotonin
Maintenance

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis. / Berglund, Eric D.; Liu, Chen; Sohn, Jong Woo; Liu, Tiemin; Kim, Mi Hwa; Lee, Charlotte E.; Vianna, Claudia R.; Williams, Kevin W.; Xu, Yong; Elmquist, Joel K.

In: Journal of Clinical Investigation, Vol. 123, No. 12, 02.12.2013, p. 5061-5070.

Research output: Contribution to journalArticle

Berglund, Eric D. ; Liu, Chen ; Sohn, Jong Woo ; Liu, Tiemin ; Kim, Mi Hwa ; Lee, Charlotte E. ; Vianna, Claudia R. ; Williams, Kevin W. ; Xu, Yong ; Elmquist, Joel K. / Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 12. pp. 5061-5070.
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