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

Academic Article
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Overview

authors

  • Xu, Baoji
  • Goulding, E. H.
  • Zang, K.
  • Cepoi, D.
  • Cone, R. D.
  • Jones, K. R.
  • Tecott, L. H.
  • Reichardt, L. F.

publication date

  • July 2003

journal

  • Nature Neuroscience  Journal

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.

subject areas

  • Aging
  • Animals
  • Behavior, Animal
  • Body Weight
  • Brain-Derived Neurotrophic Factor
  • Carrier Proteins
  • Circadian Rhythm
  • Diet, Fat-Restricted
  • Drinking
  • Eating
  • Energy Intake
  • Energy Metabolism
  • Feeding Behavior
  • Female
  • Food Deprivation
  • Gene Expression Regulation
  • Humans
  • Hypothalamic Area, Lateral
  • Hypothalamic Hormones
  • Hypothalamus, Middle
  • Immunohistochemistry
  • In Situ Hybridization
  • Injections, Intraventricular
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Melanins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Mutation
  • Nerve Tissue Proteins
  • Neurons
  • Neuropeptide Y
  • Neuropeptides
  • Obesity
  • Orexin Receptors
  • Orexins
  • Phenylalanine
  • Pituitary Hormones
  • Polyenes
  • RNA, Messenger
  • Receptor, Melanocortin, Type 4
  • Receptor, trkB
  • Receptors, Corticotropin
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Recombinant Proteins
  • Sex Characteristics
  • alpha-MSH
  • beta-Galactosidase
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Identity

PubMed Central ID

  • PMC2710100

International Standard Serial Number (ISSN)

  • 1097-6256

Digital Object Identifier (DOI)

  • 10.1038/nn1073

PubMed ID

  • 12796784
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Additional Document Info

start page

  • 736

end page

  • 742

volume

  • 6

issue

  • 7

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