Muscle Of High-fat Diet Fed Mice Research Articles

Aerobic exercise reduced the amount of CHRONO bound to BMAL1 and ameliorated glucose metabolic dysfunction in skeletal muscle of high-fat diet-fed mice

AimsThe purpose of this study was to investigate the effects of aerobic exercise on the CHRONO-BMAL1 pathway and glucose metabolism in skeletal muscle of high-fat diet (HFD)-fed mice. Main methodsMale C57BL/6J mice were randomly allocated into four groups: normal chow diet with control (NCD + CON), NCD with exercise (NCD + EXE), HFD with control (HFD + CON) and HFD with exercise (HFD + EXE). The NCD and HFD groups were respectively fed a diet of 10 % and 60 % kilocalories from fat for 12 weeks. During the dietary intervention, EXE groups were subjected to 70 % VO2max intensity of treadmill exercise six times per week for 12 weeks. Body weight, energy intake, fat weight, serum lipid profiles, systemic glucose homeostasis, the amount of CHRONO bound to BMAL1, the enzymatic activity, mRNA and protein expression involved in glucose metabolism of skeletal muscle were measured. Key findingsThe results showed that the 12-week HFD feeding without exercise induced weight gain, serum dyslipidemia and insulin resistance. Furthermore, HFD increased the amount of CHRONO bound to BMAL1 and repressed the glucose metabolism in skeletal muscle. However, aerobic exercise prevented weight gain, serum dyslipidemia and systemic insulin resistance in the HFD-fed mice. Meanwhile, aerobic exercise also decreased the amount of CHRONO bound to BMAL1 and increased the glucose uptake, glucose oxidation and glycogenesis in skeletal muscle of the HFD-fed mice. SignificanceThese data suggested that aerobic exercise could counterbalance CHRONO interacted with BMAL1 and prevent glucose metabolism dysfunction of skeletal muscle, and finally maintain whole-body insulin sensitivity in the HFD-fed mice.

Carnitine induces autophagy and restores high-fat diet-induced mitochondrial dysfunction

ObjectiveAutophagy is suppressed in skeletal muscle and the liver with insulin resistance induced by a high-fat diet. Autophagy is essential for maintaining mitochondrial function, and dysfunctional mitochondria are associated with insulin resistance. As carnitine treatment is well known to improve insulin resistance by promoting mitochondrial function, we investigated if carnitine affects autophagy in the skeletal muscle of a high-fat diet-induced rodent model of obesity. ResultsAfter 6weeks on a high-fat diet (48kcal% fat), mice developed glucose intolerance, and the gastrocnemius muscle showed a decrease in insulin signaling and mitochondrial function, which was reversed after carnitine (100mg/kg/day) treatment by oral gavage for 2weeks. Swollen mitochondria with destroyed cristae were observed in the skeletal muscle of high-fat diet-fed mice but were not there after carnitine treatment. High-fat diet decreased LC3B-II, a marker of autophagosome formation, and increased sequestosome 1 (SQSTM1), expression of which was reversed after carnitine treatment. In C2C12 myotubes, prolonged treatment with palmitate suppressed autophagy, which was relieved by carnitine treatment. However, the induction of autophagy by carnitine in C2C12 myotubes was not observed after knock-down of peroxisome proliferator-activated receptor γ (PPARγ), which is known to regulate autophagy. ConclusionWe conclude that the removal of dysfunctional mitochondria by induction of autophagy through PPARγ may be a novel mechanism by which carnitine improves insulin resistance and mitochondrial dysfunction in obesity.