Role of local muscle contractile activity in the exercise-induced increase in NR4A receptor mRNA expression.

Exercise upregulates the expression of NR4A receptors, which are involved in regulation of glucose and fatty acid utilization genes in skeletal muscle. The aims of our study were 1) to determine the role of local contractile activity on NR4A mRNA expression in skeletal muscle during exercise; and 2) to elucidate the mechanisms underlying the induction of NR4A mRNA expression in response to muscle contractile activity. Rats were subjected to an acute 3-h low-intensity swimming or a 3-h low-intensity treadmill running as a model of endurance exercise. Low-intensity swimming increased NR4A1 and NR4A3 mRNA in triceps but not in soleus muscle. Conversely, low-intensity treadmill running increased NR4A1 and NR4A3 mRNA in soleus but not in triceps muscle. NR4A mRNA increased concomitantly with reduced postexercise muscle glycogen, suggesting that gene expression of NR4A receptors occurs in muscles recruited during exercise. Furthermore, in resting rats, an acute 1-h local electrical stimulation of a motor nerve to the tibialis anterior muscle caused increases in NR4A1 and NR4A3 mRNA relative to the contralateral control muscle of the same animals. On the other hand, after 6 h of hindlimb immobilization, NR4A1 and NR4A3 mRNA were reduced in immobilized soleus muscle relative to contralateral control muscle. In addition, both NR4A1 and NR4A3 mRNA in epitrochlearis muscle were increased after 6-h incubation with 0.5 mM 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside, which activates AMP-activated protein kinase. These results suggest that 1) local muscle contractile activity is required for increased expressions of NR4A1 and NR4A3 mRNA during exercise; and 2) muscle contractile activity-induced increases in NR4A1 and NR4A3 mRNA may be mediated by AMPK activation, at least in part.