Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT(2C) receptor gene

Katsunori Nonogaki, Alison M. Strack, Mary F. Dallman, Laurence H. Tecott

Research output: Contribution to journalArticlepeer-review

391 Citations (Scopus)

Abstract

Brain serotonin and leptin signaling contribute substantially to the regulation of feeding and energy expenditure. Here we show that young adult mice with a targeted mutation of the serotonin 5-HT(2C) receptor gene consume more food despite normal responses to exogenous leptin administration. Chronic hyperphagia leads to a 'middle-aged'-onset obesity associated with a partial leptin resistance of late onset. In addition, older mice develop insulin resistance and impaired glucose tolerance. Mutant mice also responded more to high-fat feeding, leading to hyperglycemia without hyperlipidemia. These findings demonstrate a dissociation of serotonin and leptin signaling in the regulation of feeding and indicate that a perturbation of brain serotonin systems can predispose to type 2 diabetes.

Original languageEnglish
Pages (from-to)1152-1156
Number of pages5
JournalNature Medicine
Volume4
Issue number10
DOIs
Publication statusPublished - 1998 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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