DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons

Anna Santoro, Michela Campolo, Chen Liu, Hiromi Sesaki, Rosaria Meli, Zhong Wu Liu, Jung Dae Kim, Sabrina Diano

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy and glucose metabolism. Intracellular mechanisms that enable these neurons to respond to changes in metabolic environment are ill defined. Here we show reduced expression of activated dynamin-related protein (pDRP1), a mitochondrial fission regulator, in POMC neurons of fed mice. These POMC neurons displayed increased mitochondrial size and aspect ratio compared to POMC neurons of fasted animals. Inducible deletion of DRP1 of mature POMC neurons (Drp1fl/fl-POMC-cre:ERT2) resulted in improved leptin sensitivity and glucose responsiveness. In Drp1fl/fl-POMC-cre:ERT2 mice, POMC neurons showed increased mitochondrial size, ROS production, and neuronal activation with increased expression of Kcnj11 mRNA regulated by peroxisome proliferator-activated receptor (PPAR). Furthermore, deletion of DRP1 enhanced the glucoprivic stimulus in these neurons, causing their stronger inhibition and a greater activation of counter-regulatory responses to hypoglycemia that were PPAR dependent. Together, these data unmasked a role for mitochondrial fission in leptin sensitivity and glucose sensing of POMC neurons.

Original languageEnglish (US)
Pages (from-to)647-660
Number of pages14
JournalCell Metabolism
Volume25
Issue number3
DOIs
StatePublished - Mar 7 2017

Keywords

  • Drp1
  • POMC neurons
  • counter-regulatory responses to hypoglycemia
  • glucose sensing
  • leptin
  • mitochondrial fission

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Santoro, A., Campolo, M., Liu, C., Sesaki, H., Meli, R., Liu, Z. W., Kim, J. D., & Diano, S. (2017). DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons. Cell Metabolism, 25(3), 647-660. https://doi.org/10.1016/j.cmet.2017.01.003