Not only accumulation, but also saturation status of intramuscular lipids is significantly affected by PPARγ activation

Abstract

Intramuscular lipid accumulation has been associated with insulin resistance, and after thiazolidinediones (TZD) treatment, it was shown to be reduced in some, but not all, studies. This work was undertaken to investigate the relationships between intramuscular lipids [free fatty acids (FFA), diacylglycerols (DAG), triacylglycerol (TAG) and phospholipids] and plasmalemmal expression of fatty acid (FA) transporter [FAT/CD36 and FABPpm] in the muscles of varying oxidative capacity, after peroxisome proliferator-activated receptors gamma (PPARγ) activation (rosiglitazone) in an animal model of high-fat-diet-induced insulin resistance. Endurance training was also included to further explore the differences in these relationships. We have used gas liquid chromatography to estimate FA content and composition in each lipid fraction. For sarcolemmal expression of FA transporters, subfractionation of skeletal muscles with subsequent western blot technique was applied. High-fat diet induced intramuscular accumulation of FFA, DAG and TAG, irrespective of muscle's fibre composition. PPARγ activation (rosiglitazone) and, to a lesser extent, endurance training further increased TAG accumulation, while it reduced DAG in oxidative muscles (soleus and red gastrocnemius). Aforementioned interventions increased also sarcolemmal FAT/CD36 and FABPpm expressions in particular muscles. Irrespective of diet, rosiglitazone and exercise decreased significantly FA saturation status favouring proportionate enhancement in monounsaturated FA (rosiglitazone) or polyunsaturated FAs (endurance training). These findings support the conclusion that not only the change in total lipid content (DAG and TAG), but also FA composition is affected by rosiglitazone in an animal model of high-fat-diet-induced insulin resistance.