| First Author | Nonogaki K | Year | 1998 |
| Journal | Nat Med | Volume | 4 |
| Issue | 10 | Pages | 1152-6 |
| PubMed ID | 9771748 | Mgi Jnum | J:50262 |
| Mgi Id | MGI:1290118 | Doi | 10.1038/2647 |
| Citation | Nonogaki K, et al. (1998) Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene [see comments]. Nat Med 4(10):1152-6 |
| abstractText | 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 adminis-tration. 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. |
