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 combiningtwo intermittent fasting (IF) protocols, time-restricted feeding(TRF) and 5:2 IF, with exercise on the hypothalamic lipogenic pathwayvia 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-dayfood restriction followed by 5-days of ad libitum feeding), and5:2+Ex. The Ex groups swam 1h/day, 5 days/week. IF and Ex were appliedfor 8 weeks. Hypothalamic SREBP-1c and SREBP-2, acetyl-CoA carboxylase(ACC), fatty acid synthase (FAS), cholesterol, and triglyceridelevels were measured using commercial kits. IF decreased body weightin the 5:2 and 5:2+Ex groups (p <0.05) and reduced the food intake amount mainly in the 5:2 and TRFgroups. The effect of 5:2 IF on visceral fat was prominent. HypothalamicSREBP-1c levels in the Ex, TRF+Ex, 5:2, and 5:2+Ex groups and SREBP-2levels in the Ex, 5:2, and 5:2+Ex groups were higher than the Cgroup (p < 0.05). The TRF+Exand 5:2 groups had higher ACC levels than the C group (p < 0.05). While the FAS levelswere unaltered, both IF regimens increased hypothalamic triglycerideand cholesterol levels in the TRF+Ex, 5:2, and 5:2+Ex groups (p < 0.05). Both IF protocols aloneand in combination with Ex induced an increase in stomach length(p < 0.05). Our resultsdemonstrated that exercise increased hypothalamic SREBPs, whichare essential for brain development/function. 5:2 IF may be a betterdietary strategy than TRF for losing weight, lowering visceral fats,and improving hypothalamic lipogenic pathway.