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Brain-derived neurotrophic factor regula ... ream of melanocortin-4 receptor
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.
Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF
Nature neuroscience
2003-07-01 00:00
6
7
736-42
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,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,Brain-Derived Neurotrophic Factor,Carrier Proteins,Hypothalamic Hormones,Intracellular Signaling Peptides and Proteins,Melanins,Nerve Tissue Proteins,Neuropeptide Y,Neuropeptides,Pituitary Hormones,Polyenes,RNA, Messenger,Receptor, Melanocortin, Type 4,Receptors, Corticotropin,Receptors, G-Protein-Coupled,Receptors, Neuropeptide,Recombinant Proteins,alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-,cocaine- and amphetamine-regulated transcript protein,melanocrocin,orexin receptors,orexins,alpha-MSH,Phenylalanine,melanin-concentrating hormone,Receptor, trkB,beta-Galactosidase
Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA bx3georgetownedu
Nat. Neurosci.
1097-6256
10.1038/nn1073
nn1073
588
True
12796784
