Jonathon AB. Smith

Abstract The transcription factor NR4A3 is regulated by exercise and a potent modulator of skeletal muscle metabolism. We report here that physical inactivity decreased skeletal muscle NR4A3 levels, concomitant with mitochondrial function and proteostasis pathways. Silencing of NR4A3 in myotubes decreased glucose oxidation and increased lactate production. This coincided with greater signalling downstream of AMPK and elevated rates of fatty acid oxidation.

Abstract Background: The transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3) is a pleiotropic regulator of skeletal muscle metabolism. NR4A3 expression is altered in response to changes in physical activity and associated with metabolic adaptations. However, the molecular mechanisms and consequences of altered NR4A3 expression remains largely unexplored. Here, we investigated the impact of NR4A3 on human skeletal muscle remodelling.