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

Michael D. Tarpey, Kevin P. Davy, Ryan P. McMillan, Suzanne M. Bowser, Tanya M. Halliday, Nabil E. Boutagy, Brenda M. Davy, Madlyn I. Frisard, Matthew W. Hulver

Metabolic inflexibility has been implicated in the pathogenesis of obesity and the development of insulin resistance. Tarpey et al. observed elevated markers of mitophagy activity in skeletal muscle of endurance-trained runners (ET) compared with sedentary (SED) males, without a discernible difference in markers of autophagy. However, the greater content of mitophagy markers in skeletal muscle of ET individuals was not associated with a corresponding higher level of metabolic flexibility. Still, skeletal muscle metabolic flexibility increased following a high-fat meal in the ET but not SED individuals.

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.

Conclusions: 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.