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 journalArticlepeer-review

313 Scopus citations


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
Pages (from-to)576-580
Number of pages5
JournalAnnals of Neurology
Issue number4
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'The Ketogenic Diet Increases Mitochondrial Uncoupling Protein Levels and Activity'. Together they form a unique fingerprint.

Cite this