title: UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.
abstract: The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill defined. Here, we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis.
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Chitoku
authors.initials: C
authors.lastname: Toda
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Jung Dae
authors.initials: JD
authors.lastname: Kim
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Department of Biological and Environmental Sciences, University of Messina, Messina 98166, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Department of Biological and Environmental Sciences, University of Messina, Messina 98166, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Zhong-Wu
authors.initials: ZW
authors.lastname: Liu
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Department of Neuroscience, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA; Section of Comparative Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut 06520, USA. Electronic address: sabrina.diano@yale.edu.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Diano
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism; D055879:Gene Knock-In Techniques; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D017382:Reactive Oxygen Species; D000071246:Uncoupling Protein 2; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C486391:Dnm1l protein, mouse; D034281:Dynamins; D005947:Glucose