title: Endothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons.
abstract: Glucose is the primary driver of hypothalamic proopiomelanocortin (POMC) neurons. We show that endothelial hypoxia-inducible factor 1α (HIF-1α) controls glucose uptake in the hypothalamus and that it is upregulated in conditions of undernourishment, during which POMC neuronal activity is decreased. Endothelium-specific knockdown of HIF-1α impairs the ability of POMC neurons to adapt to the changing metabolic environment in vivo, resulting in overeating after food deprivation in mice. The impaired functioning of POMC neurons was reversed ex vivo or by parenchymal glucose administration. These observations indicate an active role for endothelial cells in the central control of metabolism and suggest that central vascular impairments may cause metabolic disorders.
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT luis.varela@yale.edu tamas.horvath@yale.edu.
authors.forename: Luis
authors.initials: L
authors.lastname: Varela
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Suyama
authors.affiliation: Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Marya
authors.initials: M
authors.lastname: Shanabrough
authors.affiliation: Helmholtz Diabetes Center, Helmholtz Zentrum München and Division of Metabolic Diseases, Technische Universität München, Neuherberg, Germany.
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Gao
authors.affiliation: Department of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Giordano
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT luis.varela@yale.edu tamas.horvath@yale.edu.|Helmholtz Diabetes Center, Helmholtz Zentrum München and Division of Metabolic Diseases, Technische Universität München, Neuherberg, Germany.|Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary.
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D004727:Endothelium / Q000378:metabolism*; D004734:Energy Metabolism; D005508:Food Deprivation; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D006963:Hyperphagia; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011333:Pro-Opiomelanocortin; D005947:Glucose