Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor
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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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rs10835211 (menarche P=9.4×10−6) is near BDNF, a BMI locus implicated in eating behavior and body weight regulation.
“rs10835211 (menarche P-value=9.4×10−6) is near BDNF, which is a BMI locus and is implicated in eating behavior and body weight regulation27,28.”
From Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (2010) · cites this paper as [28]
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- Authors
- Xu, B., Goulding, E. H., Zang, K., Cepoi, D., Cone, R. D., Jones, K. R., Tecott, L. H., & Reichardt, L. F.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- Oregon Health & Science University (US)
- University of Colorado Boulder (US)
- Corresponding author
- Xu, Baoji
- Reichardt, Louis F
- Venue
- Nature Neuroscience
- Published
- 2003-06-08
- Volume
- 6
- Issue
- 7
- Pages
- 736-742
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2710100
- OpenAlex
- W2157226283
- Cited by
- 896
- References
- 47
- Citations by year
- 2026: 19 · 2025: 21 · 2024: 24 · 2023: 39 · 2022: 26 · 2021: 47 · 2020: 47 · 2019: 40 · 2018: 37 · 2017: 41 · 2016: 33 · 2015: 51 · 2014: 44 · 2013: 70 · 2012: 64
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P01NS016033)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- brain-derived neurotrophic factor, melanocortin-4 receptor, energy balance, ventromedial hypothalamus, TrkB receptor, hyperphagia, obesity, high-fat diet, nutritional status, BDNF signaling
- MeSH terms
- alpha-MSH, Animals, Body Weight, Circadian Rhythm, Energy Metabolism, Feeding Behavior, Female, Hypothalamus, Middle, Male, Melanins, Receptors, Corticotropin, Brain-Derived Neurotrophic Factor, Receptor, Melanocortin, Type 4, Mice
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