Skeletal muscle autophagy and mitophagy in response to high-fat feeding and endurance training
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Obesity is associated with reduced skeletal muscle insulin sensitivity, a major risk factor for development of type II diabetes. These metabolic diseases are commonly associated with an accumulation of mitochondrial dysfunction, which is speculated to contribute toward insulin resistance. High-fat diets reduce human skeletal muscle insulin sensitivity and mitochondrial function. Conversely, endurance training increases insulin sensitivity and enhances mitochondrial performance. Recent evidence in mice has found that central mechanisms of mitochondrial quality control, autophagy and mitophagy, may be suppressed in response to excess fat intake, but upregulated following endurance exercise training. These data may provide a mechanism for dietary and exercise-mediated regulation of mitochondrial quality and metabolic function. The current study investigated the impact of an acute high-fat diet on skeletal muscle autophagy and mitophagy in sedentary, healthy, non-obese college age males'. The expression of skeletal muscle autophagy and mitophagy protein markers were analyzed in response to a high-fat meal before and after a 5-day high-fat diet. Next, we examined the differences in skeletal muscle autophagy and mitophagy protein markers, and associations with skeletal muscle metabolic flexibility between endurance-trained male runners' and sedentary, healthy, non-obese males' following an overnight fast and in response to a high-fat meal. Autophagy markers' indicated reduced autophagy activity in response to a high-fat meal and following a high-fat diet, which exacerbated the high-fat meal response. However, these data could not be confirmed due to methodological limitations. Mitophagy markers were not significantly affected by the high-fat meal or diet. There were no significant differences in the expression of autophagy protein markers between endurance-trained and sedentary groups', but mitophagy markers were significantly elevated in endurance-trained runners'. Metabolic flexibility was not significantly different between groups' following an overnight fast or in response to a high-fat meal, and was not associated with the expression of autophagy and mitophagy protein markers. In conclusion, autophagy may be suppressed by a 5-day high-fat diet, but further analysis is required for confirmation. Endurance-trained male runners show increased markers of mitophagy, which were not associated with improved metabolic flexibility while fasted or following a high-fat meal.
- Doctoral Dissertations