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

Baoji Xu, Evan H. Goulding, Keling Zang, David Cepoi, Roger D. Cone, Kevin R. Jones, Laurence H. Tecott, Louis F. Reichardt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

617 Scopus citations

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 languageEnglish (US)
Pages (from-to)736-742
Number of pages7
JournalNature neuroscience
Volume6
Issue number7
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Neuroscience(all)

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