_1–3-Adrenoreceptor (AR) deficient mice are unable to regulate energy expenditure and develop diet-induced obesity on a high fat diet. We determined previously that ₂-AR agonist treatment activated expression of the mRNA encoding the orphan nuclear receptor, NOR-1, in muscle cells and plantaris muscle. Here, we show that ₂-AR agonist treatment significantly and transiently activated the expression of NOR-1 (and the other members of the NR4A subgroup) in slow-twitch oxidative soleus muscle and fast-twitch glycolytic tibialis anterior muscle. The activation induced by -adrenergic signaling is consistent with the involvement of Protein Kinase A, MAPK and phosphorylation of cAMP response element-binding protein. Stable cell lines transfected with a siRNA targeting NOR-1 displayed decreased palmitate oxidation, and lactate accumulation. In concordance with these observations, ATP production in the NOR-1 siRNA (but not control) transfected cells was resistant to (azide-mediated) inhibition of oxidative metabolism, and expressed significantly higher levels of hypoxia inducible factor-1. In addition, we observed the repression of genes that promote (i) fatty acid oxidation [PGC-1/ and lipin1] and (ii) TCA cycle mediated carbohydrate (pyruvate) oxidation [pyruvate dehydrogenase phosphatase 1 regulatory and catalytic subunits (PDP1r and c)]. Furthermore, we observed that ₂-AR agonist administration in mouse skeletal muscle induced the expression of genes that activate fatty acid oxidation and modulate pyruvate utilization, including, PGC-1, lipin1, FOXO1, and PDK4. Finally, we demonstrate that NOR-1 is recruited to the lipin1 and PDK-4 promoters, and this is consistent with NOR-1-mediated regulation of these genes. In conclusion, NOR-1 is necessary for oxidative metabolism in skeletal muscle.