The ketogenic diet increases mitochondrial uncoupling protein levels and activity.
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.
Sullivan
Patrick G
PG
Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA.
Rippy
Nancy A
NA
Dorenbos
Kristina
K
Concepcion
Rachele C
RC
Agarwal
Aakash K
AK
Rho
Jong M
JM
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D004041:Dietary Fats / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels; D007659:Ketones / Q000494:pharmacology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D004041:Dietary Fats; D007473:Ion Channels; D007659:Ketones; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1