Exercise and Obesity-Induced Insulin Resistance in Skeletal Muscle

초록

The development of insulin resistance (IR), particularly in skeletal muscle, is closely associated with obesity and type II diabetes. Obesity-induced IR in skeletal muscle is a multifactorial process. So far, it is not clear what specific mechanism(s) are responsible for obesity-related IR. However, a number of contributing factors have been suggested. We will highlight some potential mechanisms of obesity-induced IR in skeletal muscle in terms of mitochondrial role in the cells; 1) mitochondrial-independent mechanisms including accumulations of intramyocellular lipid (IMCL) and lipid intermediates (e.g., FA-CoA, DAG, and ceramide) and 2) mitochondrial-dependent mechanisms including mitochondrial overload-related incomplete fatty acid oxidation and mitochondrial oxidative stress. Mitochondrial dysfunction is central to the pathogenesis of multiple diseases such as obesity, diabetes, aging, and cancer. Mitochondrial reactive oxygen species (ROS), a byproduct of mitochondrial oxidative phosphorylation, has been also implicated in insulin resistance in skeletal muscle. We recently found that high fat diet (HFD)-induced mitochondrial H2O2 emission was a primary factor linking excess fat intake to the development of IR in skeletal muscle. Mitigating HFD-induced H2O2 emission by high energy demand (e.g., exercise) may be a potential strategy to treat and/or prevent IR in obesity. We determined whether a daily mild increase in energy expenditure by exercise is sufficient to prevent the increase in skeletal muscle mitochondrial H2O2 emitting potential, and the decrease in insulin sensitivity induced by HFD in rodents. Young male Sprague-Dawley rats (3groups, n=10/ group) were fed a standard chow or HFD (60% of total calorie from fat) for seven weeks. The animals given HFD were also administered by low intensity treadmill exercise (15m/min, 0grade, 2h/d, 7d/wk, 7wks). Insulin resistance by oral glucose tolerance test (2g/kg) was elevated in HFD-fed rats. However