UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism*
  • Dynamins / metabolism
  • Gene Knock-In Techniques
  • Glucose / metabolism*
  • Homeostasis
  • Ion Channels / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondrial Dynamics*
  • Mitochondrial Proteins / metabolism*
  • Neurons / metabolism
  • Reactive Oxygen Species
  • Uncoupling Protein 2
  • Ventromedial Hypothalamic Nucleus / metabolism*


  • Ion Channels
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Ucp2 protein, mouse
  • Uncoupling Protein 2
  • Dnm1l protein, mouse
  • Dynamins
  • Glucose