Leptin attenuates cerebral ischemic injury in rats by modulating the mitochondrial electron transport chain via the mitochondrial STAT3 pathway

Brain Behav. 2019 Feb;9(2):e01200. doi: 10.1002/brb3.1200. Epub 2019 Jan 10.

Abstract

Background: According to recent studies, leptin may exert a neuroprotective function by affecting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). During stress, STAT3 regulates mitochondrial oxidative stress and reduces apoptosis.

Objective: In the present study, we hypothesized that leptin increases STAT3 phosphorylation in the mitochondria and protects against mitochondrial oxidative stress in rats subjected to permanent middle cerebral artery occlusion (MCAO).

Results: Leptin reduced reactive oxygen species (ROS) production, and we confirmed that the mechanism underlying this change involved the enzymatic activities of mitochondrial respiratory chain complexes I and II. In addition, leptin increased the level of STAT3 Ser727 phosphorylation in the mitochondria.

Conclusions: Based on these results, leptin may regulate mitochondrial respiratory chain enzymatic activities via mitochondria-targeted STAT3 to reduce ROS production and protect brain tissues from mitochondrial oxidative stress during cerebral ischemia.

Keywords: STAT3; cerebral ischemia; leptin; mitochondria; neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Brain Ischemia / metabolism*
  • Electron Transport / physiology*
  • Leptin / metabolism*
  • Male
  • Mitochondria* / enzymology
  • Mitochondria* / metabolism
  • Mitochondrial Proteins / metabolism
  • Neuroprotection / physiology*
  • Oxidative Stress / physiology
  • Phosphorylation
  • Rats
  • Reactive Oxygen Species / metabolism
  • STAT3 Transcription Factor / metabolism*

Substances

  • Leptin
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • STAT3 Transcription Factor