Abstract
The melanocortin-4 receptor (MC4R) is critically involved in regulating energy balance, and obesity has been observed in mice with mutations in the gene for brain-derived neurotrophic factor (BDNF). Here we report that BDNF is expressed at high levels in the ventromedial hypothalamus (VMH) where its expression is regulated by nutritional state and by MC4R signaling. In addition, similar to MC4R mutants, mouse mutants that expresses the BDNF receptor TrkB at a quarter of the normal amount showed hyperphagia and excessive weight gain on higher-fat diets. Furthermore, BDNF infusion into the brain suppressed the hyperphagia and excessive weight gain observed on higher-fat diets in mice with deficient MC4R signaling. These results show that MC4R signaling controls BDNF expression in the VMH and support the hypothesis that BDNF is an important effector through which MC4R signaling controls energy balance.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 736-742 |
| Number of pages | 7 |
| Journal | Nature neuroscience |
| Volume | 6 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2003 |
Funding
We thank M. Dalman for constructive suggestions, J. Qiu for help in dissection of fat pads, J. McKean for technical assistance and H. Chen for demonstration of implantation of osmotic pumps. E.H.G. is a Howard Hughes Medical Institute (HHMI) Physician Postdoctoral Fellow. This work has been supported by the HHMI and the National Institute of Neurological Disorders and Stroke (L.F.R.).
ASJC Scopus subject areas
- General Neuroscience
