SKELETAL-MUSCLE MEMBRANE LIPID-COMPOSITION IS RELATED TO ADIPOSITY AND INSULIN ACTION

The cellular basis of insulin resistance is still unknown, however, re lationships have been demonstrated between insulin action in muscle an d the fatty acid profile of the major membrane structural lipid (phosp holipid). The present study aimed to further investigate the hypothesi s that insulin action and adiposity are associated with changes in the structural lipid composition of the cell, In 52 adult male Pima India ns, insulin action (euglycemic clamp), percentage body fat (pFAT; unde rwater weighing), and muscle phospholipid fatty acid composition (perc utaneous biopsy of vastus lateralis) were determined, Insulin action ( high-dose clamp; MZ) correlated with composite measures of membrane un saturation (% C20-22 polyunsaturated fatty acids [r = 0.463, P < 0.001 ], unsaturation index [r = -0.369, P < 0.01]), a number of individual fatty acids and with Delta 5 desaturase activity (r = 0.451, P < 0.001 ), pFAT (range 14-53%) correlated with a number of individual fatty ac ids and Delta 5 desaturase activity (r = -0.610, P < 0.0001), Indices of elongase activity (r = -0.467, P < 0.001), and Delta 9 desaturase a ctivity (r = 0.332, P < 0.05) were also related to pFAT but not insuli n action, The results demonstrate that Delta 5 desaturase activity is independently related to both insulin resistance and obesity, While de termining the mechanisms underlying this relationship is important for future investigations, strategies aimed at restoring ''normal'' enzym e activities, and membrane unsaturation, may have therapeutic importan ce in the ''syndromes of insulin resistance.''