Abstract: To investigate the effect of intermittent fasting (IF) combined with exercise on browning of white adipose tissue (WAT), we randomly divided male C57BL/6 mice aged 5–6 weeks into six groups: control (Con), exercise (Ex), alternate-day fasting (ADF), alternate-day fasting combined with exercise (ADFEx), time-restricted feeding (TRF), and time-restricted feeding combined with exercise (TRFEx). After the six-week experimental period, blood lipid levels of mice were tested. Next, Western blot was used to detect the expression levels of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor gamma (PPARγ), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), uncoupling protein 1 (UCP1), active fibronectin type III domain containing protein 5 (FNDC5) and PR domain-containing 16 (PRDM16) in the bilateral inguinal white adipose tissue (in-WAT), perirenal adipose tissue (pe-WAT), epididymal adipose tissue (ep-WAT), interscapular brown adipose tissue (BAT), and left hindlimb skeletal muscle of mice. The effect of IF combined with exercise on protein expression in WAT browning-related signaling pathways in mice was analyzed, and the degrees of browning in different adipose tissues were compared. The results showed that the level of total cholesterol (TC) in each experimental group was significantly lower than that of the Con group. The levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in the TRF and TRFEx groups were significantly lower than those in the Con group (P < 0.05). The relative expression levels of p-AMPK, PPARγ, PGC-1α, UCP1, FNDC5 and PRDM16 in different adipose tissues and skeletal muscle increased to different extents in the ADF, ADFEx, TRF and TRFEx groups compared with the Con group; the relative expression levels of p-AMPK, PPARγ, PGC-1α and UCP1 in BAT, in-WAT and pe-WAT increased significantly in the TRFEx group compared with the Con group. These results suggested that the combination of IF and exercise promoted the browning of WAT, and the mechanism might be related to the activation of the PPARγ/PGC-1α/UCP1 signaling pathway. TRFEx was most effective among all treatments.

Key words: intermittent fasting; exercise; white adipose tissue; brown adipose tissue; browning of white adipose tissue