Effects of alternate-day fasting on high-fat diet-induced insulin resistance in rat skeletal muscle

Aims The purpose of this study was to investigate the effects of alternate-day fasting (ADF) on insulin-stimulated glucose transport activity in skeletal muscle in rats fed a high-fat diet. Main methods Male Wistar rats were placed on a high-fat diet (n = 24) or standard chow diet (Chow, n = 12) for 10 weeks. Rats fed the high-fat diet were separated into two groups after 4 weeks. One group was subjected to ADF for the subsequent 6 weeks (HF-ADF, n = 12), and the other group was maintained on an ad libitum diet (HF-AL, n = 12). After the 10-week dietary intervention, measurements of insulin-stimulated glucose uptake and insulin tolerance test (ITT) were performed. Key findings Whereas the total intra-abdominal fat mass in the HF-AL group was significantly higher than in the Chow and HF-ADF groups, there was no significant difference between the Chow and HF-ADF groups. However, insulin-stimulated glucose uptake in skeletal muscles was significantly lower in both high-fat fed groups than in the Chow group. Muscle GLUT-4 protein content in HF-AL is significantly lower (~ 30%) than in Chow, and further reduction (~ 42%) was observed in the HF-ADF group rats. The HF-ADF and HF-AL group rats had less reduction in glycemia than did the Chow group rats during ITT. Significance ADF was unable to eliminate high-fat diet-induced muscle insulin resistance, despite a substantial decrease in total intra-abdominal fat mass. This might have resulted from a reduction in GLUT-4 protein in both HF-AL and HF-ADF rats compared to the Chow group.