Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis

N Balthasar, J Rossi, DP Olson, M Scott, E Berglund, CE Lee, MJ Choi, D Lauzon, BB Lowell, JK Elmquist

Research output: Contribution to journalArticle (Academic Journal)peer-review

462 Citations (Scopus)

Abstract

Melanocortin-4 receptor (MC4R) mutations cause dysregulation of energy balance and hyperinsulinemia. We have used mouse models to study the physiological roles of extrahypothalamic MC4Rs. Re-expression of MC4Rs in cholinergic neurons (ChAT-Cre, loxTB MC4R mice) modestly reduced body weight gain without altering food intake and was sufficient to normalize energy expenditure and attenuate hyperglycemia and hyperinsulinemia. In contrast, restoration of MC4R expression in brainstem neurons including those in the dorsal motor nucleus of the vagus (Phox2b-Cre, loxTB MC4R mice) was sufficient to attenuate hyperinsulinemia, while the hyperglycemia and energy balance were not normalized. Additionally, hepatic insulin action and insulin-mediated suppression of hepatic glucose production were improved in ChAT-Cre, loxTB MC4R mice. These findings suggest that MC4Rs expressed by cholinergic neurons regulate energy expenditure and hepatic glucose production. Our results also provide further evidence of the dissociation in pathways mediating the effects of melanocortins on energy balance and glucose homeostasis.
Translated title of the contributionMelanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis
Original languageEnglish
Pages (from-to)195 - 204
Number of pages10
JournalCell Metabolism
Volume13
Issue number2
DOIs
Publication statusPublished - 2 Feb 2011

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  • RCUK FELLOW

    Ulcigrai, C. (Principal Investigator)

    1/08/071/08/12

    Project: Research

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