Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

The nuclear receptor Nor-1 is a target of exercise signalling in skeletal muscle and mediates exercise-associated metabolic phenotypes (#239)

Michael A Pearen 1 , Joel M Goode 1 , Kelvin Z Tuong , Rebecca L Fitzsimmons 1 , George EO Muscat 1
  1. Institute for Molecular Bioscience, The University Of Queensland, St Lucia, QLD, Australia

Nor-1/NR4A3 is a member of the orphan nuclear receptor 4A (NR4A) subgroup. We have previously reported that over-expression of activated Nor-1 in mouse skeletal muscle produces physical, metabolic and molecular phenotypes that are similar to the changes observed following aerobic exercise training. These phenotypes include a transition towards a type IIX oxidative skeletal muscle fibers, increased mitochondrial number, enhanced oxygen consumption, enhanced running endurance (and glycogen accumulation), enhanced glucose tolerance and decreased body adiposity (1,2). In addition to this, our current work demonstrates that over-expression of activated Nor-1 produces skeletal muscle hypertrophy and enhanced vascularisation that appears mediated by myostatin/SMAD signaling and VEGF signaling pathways respectively. Given the key similarities between the Nor-1 transgenic mouse line and changes observed following aerobic exercise training we examined Nor-1 in the context of exercise signalling. Here we report that Nor-1 mRNA expression is increased at 1 to 4 hours following exercise. The induction of Nor-1 expression by exercise is specifically initiated by skeletal muscle depolarisation, mediated by a calcium/calcineurin signalling cascade and appears to involve cAMP response element-binding protein (CREB) transactivating Nor-1. Furthermore, the induction of Nor-1 expression by exercise is unable to be blocked by the β-adrenergic antagonist propranolol and therefore appears independent of sympathetic signalling that occurs during exercise. Taken together, these results suggest that enhanced Nor-1 expression in skeletal muscle following exercise may function to mediate the positive physical, metabolic and molecular changes that occur following exercise (such as enhanced metabolic flux and glucose tolerance).

  1. Pearen et al. Transgenic muscle-specific Nor-1 expression regulates multiple pathways that effect adiposity, metabolism, and endurance. Molecular Endocrinology, 27, 1897-917.
  2. Pearen et al. The nuclear receptor, Nor-1, markedly increases type II oxidative muscle fibers and resistance to fatigue. Molecular Endocrinology, 26, 372-84.