Intermittent fasting and exercise: a dual intervention for orchestrating glycolipid conversion and utilization in healthy mice.

Intermittent fasting (IF) and exercise can reverse the impaired glycolipid conversion ability caused by obesity. However, the effects of IF and exercise combination on glycolipid conversion ability in normal individuals remain to be determined. In this study, male KM mice were subjected to IF (including alternate-day fasting (ADF), time-restricted fasting (TRF)), treadmill exercise, and a combination of the two interventions for 6 weeks. The effects of two IF models combined exercise on glycolipid conversion in mice were investigated by detecting serum biochemical indexes, and the expressions of genes and proteins closely related to the glycolipid conversion pathway in liver, gastrocnemius, and inguinal adipose tissue. The results showed that IF combined with exercise significantly reduced fasting blood glucose, glycated serum protein and liver glycogen levels in mice. TRF combined with exercise significantly decreased triglyceride levels in serum, liver and gastrocnemius. IF combined with exercise activated the ChREBP or SREBP1/FASN pathways to enhance the transcriptional activation of the glucose-mediated adipogenesis pathway, and simultaneously promoted the expression of fatty acid oxidation proteins and reduced liver gluconeogenesis genes expression, collectively improving lipid metabolic efficiency. Furthermore, IF increased the expression of glycogen turnover-related protein PPP1R3C and adipose thermogenesis-related protein UCP1 in the inguinal adipose tissue, indicating enhanced glycogen flux coordination with adipose thermogenic activation. In conclusion, IF combined with exercise orchestrates the glycolipid conversion and substrate utilization.