The prevalence of pediatric obesity and metabolic-dysfunction associated steatotic liver disease (MASLD) is increasing with a major impact on metabolic health. Pharmacological options are lacking, and the link between the liver, muscle and mitochondrial health or how early-life physical exercise affects this interaction is poorly understood. To enhance our comprehension of inter-organ crosstalk and the beneficial effects of physical exercise, we will investigate the interplay between MASLD, exercise capacity and circulating myo- and mitokines by analyzing cardiopulmonary exercise tests and biobanked serum samples from an existing unique cohort of children with obesity. Skeletal muscle mitochondrial (dys)function during lifestyle intervention will be explored using near-infrared spectroscopy in a prospective cohort. Last, we will assess the muscle-liver axis on a mechanistic level in a pediatric MASLD mouse model, in which mice will be treated with early-life exercise or a mitokone.