Rosiglitazone reduces fatty acid translocase and increases AMPK in skeletal muscle in aged rats： a possible mechanism to prevent high-fat-induced insulin resistance

Background As an agonist of peroxisome proliferator-activated receptor-gamma （PPARy）, rosiglitazone can prevent acute fatty acid-induced insulin resistance in rats, however, the precise mechanisms by which rosiglitazone alleviates insulin resistance induced by high-fat diet need to be further investigated.Methods Wistar rats aged 23-24 weeks were divided into three groups： （1） aged control group （OC）, （2） high-fat diet （HF） group and （3） high-fat diet plus rosiglitazone maleate tablets （HF＋Rosi） treatment group （n=20 in each group）. Insulin sensitivity was evaluated by conscious hyperinsulinemic-euglycemic clamp technique. mRNA levels of fatty acid translocase （FAT/CD36）, AMP-activated protein kinase α1 （AMPKα1）, AMPKα2 and acetyl CoA carboxylase （ACC） of rat skeletal muscle were determined using real-time PCR, while muscle camitine palmitoyltransferase-1 （CPT-1β） was determined using semi-quantitative PCR. Protein expression levels of FAT/CD36, AMPK phosphorylation （reflecting AMPK activity）, P-ACC （inversely related with ACC activity） and muscle CPT-1M in rat skeletal muscles were measured using Western blotting.Results Aged rats fed by diet rich in fat for more than 8 weeks led to significant increases of plasma lipids, skeletal muscle intramuscular triglyceride and long-chain fatty acyl-CoA （LCACoA） compared to aged rats fed by normal chow diet （OC） （P 〈0.05）, which might correlate with the lower （reduced by 42.4%） whole body insulin sensitivity in HF rats. FAT/CD36 protein concentrations and mRNA levels increased in untreated HF aged rats （P 〈0.01） and high-fat diet induced a significant decrease in P-AMPK, P-ACC, CPT-1M protein concentrations and AMPKα2 and CPT-1β mRNA levels in rat skeletal muscles （P 〈0.05）. No change in AMPKα1 mRNA levels was observed in the HF group.Conclusion High-fat diet in aged rats results in a lipid accumulation and subsequent insulin resistance, while rosiglitazone can alleviate the insulin resistance by reducing fatty acid uptake as well as enhancing lipometabolism.