The Nuclear hormone receptor (NR) superfamily function as ligand dependent DNA binding factors that translate endocrine, metabolic, developmental and pathophysiological signals into gene regulation. NR4A3/Nor-1 siRNA transfection into skeletal muscle cells decreased fatty acid oxidation and increased lactate accumulation (anaerobic metabolism) suggesting that Nor-1 expression is necessary for oxidative metabolism (in vitro). Recently we have developed a mouse line with expression of activated Nor-1 in muscle, this produced a transition towards a more oxidative skeletal muscle fibre type, associated with significantly improved glucose tolerance, oxygen consumption and (treadmill) endurance ¹ . New analysis of this mouse model suggests that the oxidative phenotype is associated with reduced adiposity and resistance to high-fat diet-induced obesity. Furthermore the transgenic mouse line displays increased expression of multiple genes involved in mitochondrial oxidation, the citric acid cycle, glycolysis and beta-oxidation in skeletal muscle. This data suggests that Nor-1 not only influences exercise-dependent pathways, but also produces synchronous changes in skeletal muscle energy metabolism and body composition.