Low Carbohydrate Availability Promotes a Distinct Circulating microRNA Profile 24 Hours Following Aerobic Exercise.

Low carbohydrate availability during recovery from aerobic exercise alters skeletal muscle microRNA (miRNA) profiles, which may mechanistically regulate exercise recovery. However, its impact on circulating miRNA (c-miRNA) profiles remains unclear. Purpose: This study aimed to determine the effects of low versus adequate carbohydrate availability on c-miRNA profiles during recovery from aerobic exercise. Methods: Nine males (22±4yrs, 1.81±0.09m, 83.9±11.9kg, 25.7±2.3kg/m², mean±SD) completed this randomized, crossover study consisting of two glycogen depletion trials, followed by 24 hours of isocaloric refeeding to induce low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate, 1.0 g/kg fat) carbohydrate availability. Total c-miRNA were extracted from serum 24 hours following glycogen depletion exercise. Data were log transformed and analyzed as fold change relative to AD. Bioinformatics were conducted on significant c-miRNA and associated pathways (miRTarBase/KEGG). Follow-up transfection of miR-375-3p mimic or inhibitor into C2C12 cells assessed metabolic, inflammatory, and catabolic pathways at the gene and protein levels. Results: Of the 84 miRNA assessed, miR-335-5p (-0.49±0.60; P=0.04) and miR-375-3p (-1.57±1.25; P=0.01) were significantly lower, and miR-214-3p (1.76±1.85; P=0.02) was significantly higher in AD versus LOW. In vitro experiments indicated that miR-375-3p regulates catabolic pathways at the gene and protein level. Conclusion: Low carbohydrate availability alters c-miRNA profiles, particularly miR-375-3p, which targets proteostasis and metabolism 24 hours into recovery from aerobic exercise. These findings identify unique c-miRNA targets as potential biomarkers for the mechanistic effects of low carbohydrate availability on exercise recovery.