An 8-Week Ketogenic Diet Alternated Interleukin-6, Ketolytic and Lipolytic Gene Expression, and Enhanced Exercise Capacity in Mice

Nutrients. 2018 Nov 7;10(11):1696. doi: 10.3390/nu10111696.


Adjusting dietary fat intake is reported to affect mitochondrial biogenesis and fatty acid oxidation (FAO), and thus may enhance exercise capacity. However, a high-fat diet where carbohydrate intake is not limited enough also makes it difficult for athletes to maintain weight, and may fail to force the body to utilize fat. As such, a low-carbohydrate, high-fat, ketogenic diet (KD) may be viable. We have previously reported that an eight-week KD enhances exercise capacity, and suggested the mechanism to be enhanced lipolysis and ketolysis. In the present study, we investigated how an eight-week KD alters mRNA expression during fatty acid mobilization, FAO and ketolysis. We found that an eight-week KD may remodel the lipid metabolism profile, thus contributing to influence exercise capacity. We also found that ketolysis, lipolysis and FAO adaptations may contribute to enhanced exhaustive exercise performance. Along with enhanced FAO capacity during exhaustive exercise, a KD may also alter IL-6 synthesis and secretion profile, thus contribute to fatty acid mobilization, ketolysis, lipolysis and preventing muscle damage. Both the lipid metabolism response and IL-6 secretion appeared to be muscle fiber specific. Taken together, the previous and present results reveal that an eight-week KD may enhance exercise performance by up-regulating ketolysis and FAO ability. Therefore, a KD may have the potential to prevent muscle damage by altering IL-6 secretion profile, indicating that a KD may be a promising dietary approach in endurance athletes, sports, and for injury prevention.

Keywords: IL-6; keto-adaptation; ketogenic diet; lipid metabolism.

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Adiposity
  • Animals
  • Diet, Ketogenic*
  • Fatty Acids, Nonesterified / blood
  • Gene Expression Regulation
  • Glycogen / metabolism
  • Interleukin-6 / blood*
  • Lipid Metabolism / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / metabolism
  • Physical Conditioning, Animal*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Fatty Acids, Nonesterified
  • Interleukin-6
  • RNA, Messenger
  • interleukin-6, mouse
  • Glycogen
  • 3-Hydroxybutyric Acid