The Orphan Nuclear Receptor, NOR-1, a Target of β-Adrenergic Signaling, Regulates Gene Expression that Controls Oxidative Metabolism in Skeletal Muscle

• DOI: 10.1210/en.2007-1202
• Publication Date: 2008-03-07T01:44:48Z
• Authors: Michael A. Pearen; Stephen A. Myers; Suryaprakash Raichur; James G. Ryall; Gordon S. Lynch; George E. O. Muscat
• Keywords: PDK4; FOXO1

β1–3-Adrenoreceptor (AR)-deficient mice are unable to regulate energy expenditure and develop diet-induced obesity on a high-fat diet. We determined previously that β2-AR agonist treatment activated expression of the mRNA encoding orphan nuclear receptor, NOR-1, in muscle cells plantaris muscle. Here we show significantly transiently NOR-1 (and other members NR4A subgroup) slow-twitch oxidative soleus fast-twitch glycolytic tibialis anterior The activation induced by β-adrenergic signaling is consistent with involvement protein kinase A, MAPK, phosphorylation cAMP response element-binding protein. Stable cell lines transfected silent interfering RNA targeting displayed decreased palmitate oxidation lactate accumulation. In concordance these observations, ATP production (but not control)-transfected was resistant (azide-mediated) inhibition metabolism expressed higher levels hypoxia inducible factor-1α. addition, observed repression genes promote fatty acid (peroxisomal proliferator-activated receptor-γ coactivator-1α/β lipin-1α) trichloroacetic cycle-mediated carbohydrate (pyruvate) [pyruvate dehydrogenase phosphatase 1 regulatory catalytic subunits (pyruvate phosphatases-1r -c)]. Furthermore, administration mouse skeletal activate modulate pyruvate use, including PGC-1α, lipin-1α, FOXO1, PDK4. Finally, demonstrate recruited lipin-1α PDK-4 promoters, this NOR-1-mediated regulation genes. conclusion, necessary for