Muscle transcriptome at rest and during recovery from running in elite male ultra-endurance athletes acclimated to a high-carbohydrate versus low-carbohydrate diet

Low-carbohydrate diets enhance lipid metabolism and decrease reliance on glucose oxidation in athletes, but the associated gene expression patterns remain unclear. To provide mechanistic insight, we investigated the skeletal muscle transcriptome in elite ultra-endurance athletes habitually consuming a high-carbohydrate (HC, n=10, 33±6y, VO2max=63.4±6.2 mL O2•kg-1•min-1) or low-carbohydrate (LC, n=10, 34±7y, VO2max=64.7±3.7 mL O2•kg-1•min-1) diet. Skeletal muscle gene expression was measured at baseline (BL), immediately-post (H0), and 2h (H2) after 3h submaximal treadmill running. Exercise induced a coordinated but divergent expression pattern. LC had higher expression of genes associated with lipid metabolism, particularly at BL. At H2, gene expression patterns were associated with differential pathway activity, including inflammation/immunity, suggesting a diet-specific influence on early muscle recovery. These results indicate that a habitual ketogenic diet leads to differences in resting and exercise-induced skeletal muscle gene expression patterns, underlying our previous findings of differential fuel utilization during exercise in elite male ultra-endurance athletes. Overall design: Highly trained male ultra-endurance athletes acclimated to either high-carbohydrate or low-carbohydrate (ketogenic) diet performed a 3h treadmill run. Skeletal muscle gene expression was measured via RNA-seq on muscle biopsies collected at rest (baseline, BL), immediately post-exercise (h0), and two hours into early recovery (h2).