Effects of fructose and troglitazone on phospholipid fatty acid composition in rat skeletal muscle

Skeletal muscle phospholipid fatty acid (PLFA) composition is associated wi th insulin sensitivity in animal models and in man. However, it is not clea r whether changes in insulin sensitivity cause a change in PLFA composition or Vice versa. The present studies have examined the effects of agents kno wn to increase or decrease insulin sensitivity on PLFA composition of the m ajor phospholipids, phosphalidylcholine (PC) and phosphatidylethanolamine ( PE), in soleus and extensor digitorum longus muscle. Four groups of Sprague -Dawley rats-control, 0.2% troglitazone (Tgz), 60% fructose fed, and fructo se + Tgz-were treated for 3 wk. Fructose feeding was associated with a decr ease in muscle membrane polyunsaturated fatty acids (PUFA) and n-3 fatty ac ids in both PC and PE. Administration of Tgz alone resulted in an increase in liver (3.75 +/- 0.93 to 6.93 +/- 1.00 mu mol/min/mg tissue, P < 0.05) an d soleus muscle (0.34 +/- 0.03 to 0.67 +/- 0.09 <mu>mol/min/mg, P < 0.01) e longase activity, which would be expected to increase membrane PUFA. Howeve r, Tgz decreased PLFA associated with greater insulin sensitivity (e.g., PU FA and n-3 fatty acids) and increased PLFA associated with decreased insuli n sensitivity (16:0 and n-6 fatty acids) in both PC and PE. Go-administrati on of fructose and Tgz did not reverse the decrease in PU FA observed with fructose alone. We conclude that the improvement in insulin sensitivity rep orted with Tgz is associated with an apparently paradoxical effect to decre ase PU FA and n-3 PLFA composition in rat skeletal muscle. These studies su ggest that Tgz-mediated increases in insulin sensitivity do not result in i mproved PLFA composition.