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Article
Nature Neuroscience  6, 736 - 742 (2003)
Published online: 8 June 2003; | doi:10.1038/nn1073

Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor

Baoji Xu1, 5, Evan H Goulding2, Keling Zang1, David Cepoi3, Roger D Cone3, Kevin R Jones4, Laurence H Tecott2 & Louis F Reichardt1

1  Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.

2  Center for Neurobiology and Psychiatry, University of California, San Francisco, California 94143, USA.

3  Vollum Institute, Oregon Health and Science University, Portland, Oregon 97201, USA.

4  Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.

5  Present address: Department of Pharmacology, Georgetown University Medical Center, SE402 Medical/Dental Building, 3900 Reservoir Rd. NW, Washington, DC 20057, USA.

Correspondence should be addressed to Baoji Xu bx3@georgetown.edu or Louis F Reichardt lfr@cgl.ucsf.edu
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.

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Nature Neuroscience
ISSN: 1097-6256
EISSN: 1546-1726
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