Skeletal Muscle Hne Is Related To Insulin Resistance In Sedentary Individuals

The relationships among skeletal muscle lipid peroxidation (HNE), intramyocellular lipid content (IMCL), and insulin sensitivity were studied in sedentary adults. We assessed IMCL, glucose uptake (GDR), homeostasis model assessment index (HOMA), BMI, body fat (DXA), waist girth (WAIST), and skeletal muscle HNE adducts in 9 insulin‐sensitive (IS), 13 insulin‐resistant (IR), and 10 adults with type 2 diabetes (DB). GDR and HOMA differed among IS, IR, and DB (GDR: 16.6 ±2.6, 9.3 ± 1.6, 6.6 ± 2.1, p < 0.01; HOMA: 2.0 ± 0.7, 5.2 ± 3.7, 7.0 ± 5.1, p < 0.05. HNE was higher in DB than IS (971 ± 436 vs. 609 ± 170; p < 0.05) and correlated with GDR (R = −0.43, p < 0.05), HOMA (R = 0.43, p < 0.05), and BMI (R = 0.42, p < 0.05), but not with IMCL, WAIST, or DXA. IMCL was higher in DB than in IS and IR (8.1 ± 3.8 vs. 2.0 ± 1.0 and 3.8 ± 2.8, p < 0.01) and correlated with GDR (R = −0.56, p < 0.01). IMCL was the primary predictor of GDR (R 2 = 0.31, p < 0.01), while HNE was that of HOMA (R 2 = 0.18, p < 0.05). Our data show that (1) skeletal muscle HNE and IMCL are both determinants of the severity of insulin resistance assessed by hyperinsulinemic clamp or HOMA in sedentary adults; (2) HNE and IMCL are not related and thus impact GDR independently. These results reveal, for the first time, a negative relationship between skeletal muscle HNE and insulin sensitivity in sedentary individuals and underscore the importance of lipid peroxidation in insulin resistance. Funded by NIH (DK‐038764, HL‐055782), Department of Veterans Affairs (Merit Review), and Gatorade Sport Science Institute's Student Grant Program.