Gender factors affect fatty acids-induced insulin resistance in nonobese humans: Effects of oral steroidal contraception

Plasma free fatty acids and intramyocellular triglycerides (IMCL) content m odulate whole body insulin sensitivity in humans. To test whether the inter actions between fatty acid metabolism and insulin action in nonobese humans are related to gender factors, we studied 15 young, normal weight, healthy men and 15 women matched for life habits and whole body insulin sensitivit y, determined with the euglycemic-hyperinsulinemic clamp, by means of indir ect calorimetry to assess substrate oxidation, localized H-1 nuclear magnet ic resonance spectroscopy of calf muscles to assess IMCL content, and dual energy x-ray absorption to assess body composition In addition, to test whe ther perturbation of the feminine hormonal milieu modifies these interactio ns, we studied 15 matched females using oral steroidal contraception (OSC), Insulin sensitivity in women,. notwithstanding increased body fatness, pla sma free fatty acids, IMCL content, and circulating beta -hydroxybutyrate l evels and reduced lipid oxidation, was similar to that in men. Women using OSC showed a 40% reduction of insulin sensitivity associated with increased plasma free fatty acids, beta -hydroxybutyrate, cholesterol, and triglycer ides levels and a slight increment in IMCL content compared with women with intact hormonal cycles. In all groups the IMCL content was inversely relat ed to insulin sensitivity. In conclusion, nonobese, healthy, young women ar e as insulin sensitive as men, notwithstanding the higher levels of postabs orptive circulating and tissue-stored fatty acids; OSC-induced insulin resi stance is associated with abnormal fatty acid metabolism and loss of this g ender-related feature.