title: Regulation of Energy Balance via BDNF Expressed in Nonparaventricular Hypothalamic Neurons.
abstract: Brain-derived neurotrophic factor (BDNF) expressed in the paraventricular hypothalamus (PVH) has been shown to play a key role in regulating energy intake and energy expenditure. BDNF is also expressed in other hypothalamic nuclei; however, the role in the control of energy balance for BDNF produced in these structures remains largely unknown. We found that deleting the Bdnf gene in the ventromedial hypothalamus (VMH) during embryogenesis using the Sf1-Cre transgene had no effect on body weight in mice. In contrast, deleting the Bdnf gene in the adult VMH using Cre-expressing virus led to significant hyperphagia and obesity. These observations indicate that the lack of a hyperphagia phenotype in the Sf1-Cre/Bdnf mutant mice is likely due to developmental compensation. To investigate the role of BDNF expressed in other hypothalamic areas, we employed the hypothalamus-specific Nkx2.1-Cre transgene to delete the Bdnf gene. We found that the Nkx2.1-Cre transgene could abolish BDNF expression in many hypothalamic nuclei, but not in the PVH, and that the resulting mutant mice developed modest obesity due to reduced energy expenditure. Thus, BDNF produced in the VMH plays a role in regulating energy intake. Furthermore, BDNF expressed in hypothalamic areas other than PVH and VMH is also involved in the control of energy expenditure.
authors.affiliation: College of Animal Science and Technology (H.Y., C.S.), Northwest A&F University, Yangling, Shaanxi 712100, China; and Department of Neuroscience (H.Y., J.J.A., B.X.), The Scripps Research Institute Florida, Jupiter, Florida 33458.
authors.forename: Haili
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Animal Science and Technology (H.Y., C.S.), Northwest A&F University, Yangling, Shaanxi 712100, China; and Department of Neuroscience (H.Y., J.J.A., B.X.), The Scripps Research Institute Florida, Jupiter, Florida 33458.
authors.forename: Juan Ji
authors.initials: JJ
authors.lastname: An
authors.affiliation: College of Animal Science and Technology (H.Y., C.S.), Northwest A&F University, Yangling, Shaanxi 712100, China; and Department of Neuroscience (H.Y., J.J.A., B.X.), The Scripps Research Institute Florida, Jupiter, Florida 33458.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: College of Animal Science and Technology (H.Y., C.S.), Northwest A&F University, Yangling, Shaanxi 712100, China; and Department of Neuroscience (H.Y., J.J.A., B.X.), The Scripps Research Institute Florida, Jupiter, Florida 33458.
authors.forename: Baoji
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002149:Energy Intake / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006963:Hyperphagia / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D000072260:RNA Splicing Factors / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1 / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000072260:RNA Splicing Factors; D000074482:Thyroid Nuclear Factor 1