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

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Abstract 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.