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Cell. 2016 Feb 25;164(5):872-83. doi: 10.1016/j.cell.2016.02.010.

UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.

Author information

1
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.
2
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.
3
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.
4
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.

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.

PMID:
26919426
PMCID:
PMC4770556
[Available on 2017-02-25]
DOI:
10.1016/j.cell.2016.02.010
[Indexed for MEDLINE]
Free PMC Article

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