Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal

Objective: We tested the hypothesis that skeletal muscle of endurance-trained male runners would exhibit elevated autophagy and mitophagy markers, which would be associated with greater metabolic flexibility following a high-fat meal (HFM). Methods: Muscle biopsies were collected to determine differences in autophagy and mitophagy protein markers and metabolic flexibility under fasting conditions and 4 h following a HFM between endurance-trained male runners (n =10) and sedentary, non-obese controls (n = 9). Results: Maximal oxygen consumption (ml・kg・min⁻¹) was approximately 50% higher (p < 0.05) in endurance-trained runners compared with sedentary controls (65.8 ±2.3 and 43.1 ±3.4, respectively). Autophagy markers were similar between groups. Mitophagy and mitochondrial dynamics protein markers were significantly higher in skeletal muscle of endurance-trained runners compared with sedentary controls in the fasted state, although unaffected by the HFM. Skeletal muscle metabolic flexibility was similar between groups when fasted (p > 0.05), but increased in response to the HFM in endurance-trained athletes only (p < 0.005). Key mitophagy markers, phospho-Pink1Thr257 and phospho- ParkinS⁶⁵(r = 0.64, p < 0.005), and phospo-ParkinSer⁶⁵ and phospho-Drp1Ser⁶¹⁶ (r = 0.70, p < 0.05) were correlated only within the endurance-trained group. Autophagy and mitophagy markers were not correlated with metabolic flexibility. Conclusion: In summary, mitophagy may be enhanced in endurance-trained runners based on elevated markers of mitophagy and mitochondrial dynamics. The HFM did not alter autophagy or mitophagy in either group. The absence of a relationship between mitophagy markers and metabolic flexibility suggests that mitophagy is not a key determinant of metabolic flexibility in a healthy population, but further investigation is warranted.