Alternate-day High-fat Diet Feeding Induces Insulin resistance Despite No Abdominal Fat Accumulation And Mitochondrial Dysfunction

Abstract

It has been hypothesized that insulin resistance in skeletal muscle is mediated by abdominal fat accumulation or deficiency of mitochondria. In contrast, we found that intermittent fasting (fasting every other day) that causes a reduction of abdominal fat mass results in insulin resistance in skeletal muscle. This result suggests that abdominal fat accumulation is not always associated with insulin resistance. PURPOSE:To examine the effect of alternate-day high-fat diet feeding on insulin resistance, accumulation of abdominal fat mass and mitochondrial dysfunction. METHODS:Four-week old male Wistar rats were divided into control (CON), high-fat diet (HFD) and alternate-day high-fat diet (ALT) groups. CON and HFD groups were fed a standard chow diet or high-fat diet for 4 weeks, respectively. ALT group was fed a standard chow diet and high-fat diet every other day for 4 weeks. After the dietary intervention, an oral glucose tolerance test was performed. RESULTS: Epididymal fat mass in the HFD group was higher than those of CON and ALT groups (CON: 3.1 g, HFD: 5.1 g, ALT: 3.9 g). Beta-hydroxyacyl CoA dehydrogenase activities in plantaris muscle of rats in HFD and ALT rats were significantly higher than that in CON rats, whereas there was no difference between HFD and ALT group (CON: 8.2 μmol/min/g, HFD: 11.2 μmol/min/g, ALT: 10.1 μmol/min/g). The plasma insulin concentrations before glucose administration was significantly lower ALT group than those of CON and HFD groups (CON: 96.9 mg/dL, HFD: 96.8 mg/dL, ALT: 81.1 mg/dL). However, the area under the curve for plasma glucose during the OGTT was significantly higher in ALT group that of CON group (CON: 1949 mg/dL•min, HFD: 2713 mg/dL•min, ALT:3398 mg/dL•min). CONCLUSIONS:These results suggest that alternate-day high-fat diet feeding induces insulin resistance without accumulation of abdominal fat or mitochondrial deficiency.