The ketogenic diet increases mitochondrial uncoupling protein levels and activity

Abstract

Fatty acids are known to enhance mitochondrial uncoupling protein (UCP) activity. We asked whether a high‐fat ketogenic diet (KD) increases UCP levels and activity in hippocampi of juvenile mice. Maximum mitochondrial respiration rates were significantly (p < 0.001) higher in KD‐ versus standard diet (SD)–treated animals, indicating increased UCP‐mediated proton conductance that can reduce reactive oxygen species (ROS) production. Western blots showed significant (p < 0.05) or borderline significant increases in UCP2, UCP4, and UCP5 protein levels, and increased immunoreactivity to these three UCP isoforms was most prominently seen in the dentate gyrus of KD‐fed mice. Finally, we found that oligomycin‐induced ROS production was significantly (p < 0.05) lower in KD‐fed mice than in SD controls. Collectively, our data suggest that a KD may exert neuroprotective effects by diminishing ROS production through activation of mitochondrial UCPs.