LXR activation prevents exhaustive exercise-induced hypoglycaemia and spares muscle glycogen but does not enhance running endurance in untrained rats

Aim: Liver X receptors (LXRs) are ligand-activated transcription factors that play an important role in regulation of hepatic lipid and carbohydrate metabolism. However, to date there is very few information on the role of LXRs in skeletal muscle. Moreover, it remains obscure whether LXR activation affects physical endurance. Therefore, we aimed to examine effects of selective LXR activator - T0901317 - on running endurance and skeletal muscle exercise metabolism in rats. Methods: The animals were assigned to two groups (n = 20) receiving either vehicle or T0901317 (10 mg kg-1 day-1) for 1 week. One day after the final administration, half of the rats in each group were exercised until exhaustion on the electrically driven treadmill. All animals were then anaesthetized and samples of the soleus, red and white sections of the gastrocnemius muscle, epididymal fat pad and liver were excised. Results: We found that LXR activation prevented exhaustive exercise-induced hypoglycaemia. T0901317 also shifted substrate utilization in working muscles in favour of fatty acids as indicated by its glycogen sparing effect, enhanced consumption of intramuscular triacylglycerol and upregulation of genes promoting fatty acid oxidation and suppressing carbohydrate oxidation. However, running time to exhaustion was not improved. Conclusion: We conclude that LXR activation increases fatty acid utilization during exercise which, however, does not translate into measurable enhancement of exercise endurance.