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- Title
Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT<sub>2C</sub> receptor gene.
- Authors
Nonogaki, Katsunori; Strack, Alison M.; Dallman, Mary F.; Tecott, Laurence H.
- 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-HT2C 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.
- Subjects
SEROTONIN; TYPE 2 diabetes; LEPTIN
- Publication
Nature Medicine, 1998, Vol 4, Issue 10, p1152
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/2647