Effects of 5:2 Intermittent Fasting and Time-Restricted Feeding, Alone and in Combination with Swimming Exercise on Hypothalamic Lipid Homeostasis in Rats

The aim of this study was to investigate the effect of combining two intermittent fasting (IF) protocols, time-restricted feeding (TRF) and 5:2 IF, with exercise on the hypothalamic lipogenic pathway via sterol regulatory element-binding protein (SREBP)-1c and SREBP-2. Sixty male Wistar rats were divided into six groups: control (C), exercise (Ex), TRF (8h-ad libitum/ 16h-fasting), TRF+Ex, 5:2 (2-day food restriction followed by 5-days of ad libitum feeding), and 5:2+Ex. The Ex groups swam 1h/day, 5 days/week. IF and Ex were applied for 8 weeks. Hypothalamic SREBP-1c and SREBP-2, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), cholesterol, and triglyceride levels were measured using commercial kits. IF decreased body weight in the 5:2 and 5:2+Ex groups (p < 0.05) and reduced the food intake amount mainly in the 5:2 and TRF groups. The effect of 5:2 IF on visceral fat was prominent. Hypothalamic SREBP-1c levels in the Ex, TRF+Ex, 5:2, and 5:2+Ex groups and SREBP-2 levels in the Ex, 5:2, and 5:2+Ex groups were higher than the C group (p < 0.05). The TRF+Ex and 5:2 groups had higher ACC levels than the C group (p < 0.05). While the FAS levels were unaltered, both IF regimens increased hypothalamic triglyceride and cholesterol levels in the TRF+Ex, 5:2, and 5:2+Ex groups (p < 0.05). Both IF protocols alone and in combination with Ex induced an increase in stomach length (p < 0.05). Our results demonstrated that exercise increased hypothalamic SREBPs, which are essential for brain development/function. 5:2 IF may be a better dietary strategy than TRF for losing weight, lowering visceral fats, and improving hypothalamic lipogenic pathway.