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

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.