The Ketogenic Diet Increases Mitochondrial Uncoupling Protein Levels and Activity

Patrick G. Sullivan, Nancy A. Rippy, Kristina Dorenbos, Rachele C. Concepcion, Aakash K. Agarwal, Jong M. Rho

Research output: Contribution to journalArticle

242 Scopus citations

Abstract

Fatty acids are known to enhance mitochondrial uncoupling protein (UCP) activity. We asked whether a highfat 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.

Original languageEnglish (US)
Pages (from-to)576-580
Number of pages5
JournalAnnals of Neurology
Volume55
Issue number4
DOIs
StatePublished - Apr 1 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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    Sullivan, P. G., Rippy, N. A., Dorenbos, K., Concepcion, R. C., Agarwal, A. K., & Rho, J. M. (2004). The Ketogenic Diet Increases Mitochondrial Uncoupling Protein Levels and Activity. Annals of Neurology, 55(4), 576-580. https://doi.org/10.1002/ana.20062