Liver X receptor agonist T0901317 enhanced peroxisome proliferator-activated receptor-delta expression and fatty acid oxidation in rat skeletal muscle

Liver x receptors (lxr) have been characterized as key transcriptional regulators of hepatic lipid and carbohydrate metabolism. lxr are expressed also in skeletal muscle,however,their role in this tissue is poorly investigated and the vast majority of available data comes from studies on cultured myotubes. therefore,we aimed to examine effects of in vivo lxr activation on muscle lipid metabolism. the experiments were performed on male wistar rats fed on a standard rodent chow. the animals were divided into two groups (n=10) receiving either lxr activator (t0901317,10 mg/kg/day) or vehicle for one week. samples of the soleus as well as red and white sections of the gastrocnemius muscle were excised. t0901317 increased muscle expression of peroxisome proliferator-activated receptor-δ and its target genes involved in fatty acid uptake and oxidation. in addition,lxr agonist enhanced palmitate oxidation (by 55%) in isolated soleus muscle. however,palmitate incorporation into triacylglycerol was decreased (by 38%),which was associated with reduced diacylglycerol acyltransferase expression (by 66%). despite markedly increased plasma lipid concentration upon t0901317 treatment,muscle triacylglycerol level was elevated only in the red section of the gastrocnemius muscle. we conclude that t0901317 enhances muscle fatty acid oxidation,which prevents overt accumulation of intramuscular lipids that could be expected considering t0901317-induced hyperlipidemia.