Proteomics analyses of subcutaneous adipocytes reveal novel abnormalities in human insulin resistance

Objective: To provide a more global view of adipocyte changes in human insulin resistance by proteomics analyses. Methods: Baseline biopsies of abdominal subcutaneous adipose tissue were obtained from 23 subjects without diabetes. Euglycemic clamps were used to divide subjects into an insulin-resistant group (IR, N = 10) and an insulin-sensitive (IS, N = 13) group, which were of similar age and gender but unequal adiposity (greater in IR). Proteins of isolated adipocytes were quantified by mass spectrometry using normalized spectral abundance factors. Results: Of 1,245 proteins assigned, 30 were detected in at least 12 of the 23 subjects that differed significantly in abundance ≥1.5-fold between IR and IS. IR displayed a pattern of increased cytoskeletal proteins and decreased mitochondrial proteins and FABP4 and FABP5. In subgroup analyses of adiposity-matched subjects, several of these changes were less pronounced in IR, but the abundance of proteins related to lipid metabolism and the unfolded/misfolded protein response were significantly and unfavorably altered. Conclusions: These results confirm lower abundance of mitochondrial proteins and suggest increased cytoskeletal proteins and decreased FABP4 and FABP5 in subcutaneous adipocytes of typical IR individuals. Changes in proteins related to lipid metabolism and the unfolded/misfolded protein may discriminate IR and IS individuals of equal adiposity.