OBJECTIVE: Liver mitochondria adapt to high calorie intake. We investigated how exercise alters the early compensatory response of mitochondria and thus prevents fatty liver disease as a long-term consequence of overnutrition. METHODS: We compared the effects of a steatogenic high-energy diet (HED, for 6 weeks) on mitochondrial metabolism of sedentary and treadmill-trained C57BL/6N mice. We applied multi-OMICs analyses to study the alterations in the proteome, transcriptome and lipids in isolated mitochondria of liver and skeletal muscle as well as in whole tissue and examined the functional consequences by high resolution respirometry. RESULTS: HED increased the respiratory capacity of isolated liver mitochondria, both in sedentary and in ...