Background: Intermittent fasting (IF) has been known to increase insulin sensitivity and lower body weight. However, the underlining mechanism for the beneficial effects has not been elucidated enough.

Design and Method: Mice were subjected to a severe IF regimen, in which they were fasted for 72 hours and refed ad libitum for subsequent 96 hours. This cycle was consecutively repeated 4 times to enforce the effects. After 4 cycles of the IF regimen, mice were fed a high-fat diet (HFD) ad-libitum for subsequent 4 weeks of observational period. At the 2 different time points: just after 4 cycles of the IF regimen and after subsequent 4 weeks of observational ad-libitum feeding period, the physical performance was examined.

Result: Glucose tolerance tests showed a significant decrease in the glucose level of IF group just after 4 cycles of the IF regimen. In PCR analysis, expressions of genes responsible for fat oxidation and mitochondrial activation (ACO et al.) were significantly increased in the muscle. The histone acetylation in the promoter region of these mitochondria activating genes was augmented and suggested the significance for enhancement of the expressions of these genes. In addition, we found that exercise endurance was improved in the IF group, without a change in the grip power. After subsequent 4 weeks of observational feeding period, the BW in IF group was significantly lower than ad-libitum feeding group. At the time-point, the exercise endurance, glucose tolerance, histone acetylation and expression of genes maintained the similar changes observed just after 4 cycles of the IF regimen.

Conclusion: The 72 hours fasting IF regimen augmented histone acetylation in the promoter regions of mitochondrial activating genes in the muscle and adipose tissues that would accounts for the prolonged enhancement of the expression. We found that not only glucose tolerance but also exercise endurance was improved through the IF procedure.


K. Miyashita: Research Support; Self; Johnson & Johnson, Merck & Co., Inc., Novo Nordisk Inc.

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