Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man

The fatty acid composition of skeletal muscle cell membrane phospholipids ( PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particu lar importance in this relationship. Efforts to alter the PL fatty acid com position in animal models have demonstrated induction of insulin resistance . However, it has been more difficult to determine if changes in insulin se nsitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known t o induce insulin resistance in man, 9 normal subjects were studied before a nd after treatment for 1 month. Skeletal muscle membrane fatty acid composi tion of PC and PE from biopsies of vastus lateralis was correlated with ins ulin responsiveness using a 3-step hyperinsulinemic-euglycemic clamp. Treat ment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 +/- 7.5 to 64.6 +/- 9.0 mu U/mL, P < .05), cons istent with decreased peripheral insulin sensitivity. Significant changes i n the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% +/- 0.3% to 21. 7% +/- 0,4%, P < .05) and decreases in 18:0 (6.2% +/- 0.5% to 5.1% +/- 0.4% , P = .01), long-chain n-3 fatty acids (1.7% +/- 0.2% to 1.4% +/- 0.1%, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7% +/- 0.8% to 8.0% +/- 0.8%, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was sig nificantly correlated with the change in PUFAs (r = -.65, P < .05). These s tudies suggest that the induction of insulin resistance with NA is associat ed with changes in the fatty acid composition of PC in man. Copyright (C) 2 000 by W. B. Saunders Company.