Platelet Mitochondrial Bioenergetics in Adolescents at Risk of MASLD Following High-Intensity Interval Training

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent cardiometabolic disorder in adolescents with obesity associated with insulin resistance, dyslipidemia, and increased cardiovascular disease risk. Platelets contribute to inflammatory and vascular processes implicated in cardiometabolic disease, yet little is known regarding platelet mitochondrial bioenergetics in adolescents at risk for MASLD or their response to exercise training. This study characterized platelet mitochondrial respiration in adolescents at risk of MASLD and examined the effects of four weeks of high-intensity interval training (HIIT) according to MASLD status (n=10 MASLD; n=17 non-MASLD). MASLD was defined as intrahepatic triglyceride (IHTG) content ≥5% by magnetic resonance imaging. Platelet mitochondrial respiration was assessed at enrollment and after four weeks of supervised HIIT using high-resolution respirometry. Associations with cardiometabolic and fitness markers were examined using Spearman correlations, and longitudinal changes following HIIT were analyzed using generalized estimating equation models. Adolescents were 15.4±1.5 years old and 48% were boys. At enrollment, adolescents with MASLD had higher IHTG than those without MASLD (7.39±2.67% vs. 3.02±1.13%, p=0.0002). Maximal electron transfer capacity was positively associated with IHTG (rho=0.50, p=0.008) and HOMA-IR (rho=0.44, p=0.021) and inversely associated with leptin (rho=-0.60, p=0.001). Adolescents with MASLD exhibited higher NADH-linked respiration (β=0.053, p=0.033) and succinate-supported respiration (β=0.070, p=0.012). Significant time-by-MASLD interactions demonstrated reductions in both respiration measures following HIIT only in adolescents with MASLD. In conclusion, platelet mitochondrial respiration was associated with hepatic fat content and markers of metabolic dysfunction in adolescents with obesity. HIIT was associated with differential platelet bioenergetic adaptations according to MASLD status.