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Comparative Study
. 2004 Apr;55(4):576-80.
doi: 10.1002/ana.20062.

The Ketogenic Diet Increases Mitochondrial Uncoupling Protein Levels and Activity

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Comparative Study

The Ketogenic Diet Increases Mitochondrial Uncoupling Protein Levels and Activity

Patrick G Sullivan et al. Ann Neurol. .

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.

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