Succinate Modulation as a Novel Mechanism Underlying the Effects of Intermittent Fasting on Brain Function and Metabolism in Diet-Induced Obesity

Intermittent fasting (IF) shows promise for improving peripheral and CNS health, but its mechanisms are unclear. Using a diet-induced obesity mouse model (10 weeks high fat diet (HFD), then 4 weeks intervention), we compared HFD, HFD-IF, ad libitum control chow (CC), and CC-IF groups.

Switching to CC or IF reduced body weight, fat mass, and improved glucose tolerance. Notably, CC-IF uniquely enhanced exploration and reduced anxiety-like behavior. Transcriptomics revealed HFD-induced hippocampal neuroinflammation, while metabolomics identified a specific succinate signature in CC-IF mice: plasma concentration decreased while liver and brown adipose tissue (BAT) levels increased.