Insulin resistance underlies metabolic disease. Visceral, but not subcutaneous, white adipose tissue (WAT) has been linked to the development of insulin resistance, potentially due to differences in regulatory protein abundance. Here we investigate how protein levels are changed in insulin resistance in different WAT depots by developing a targeted proteomics approach to quantitatively compare the abundance of 42 nuclear proteins in subcutaneous and visceral WAT from a commonly-used insulin resistant mouse model, Lepr(db/db), and from C57BL/6J control mice. The most differentially-expressed proteins were important in adipogenesis, as confirmed by siRNA-mediated depletion experiments, suggesting a defect in adipogenesis in visceral, but not subcutaneous, insulin-resistant WAT. Furthermore, differentiation of visceral, but not subcutaneous, insulin-resistant stromal vascular cells (SVC) was impaired. In an in vitro approach to understand the cause of this impaired differentiation, we compared insulin-resistant visceral SVC to preadipocyte cell culture models made insulin-resistant by different stimuli. The insulin-resistant visceral SVC protein abundance profile correlated most with preadipocyte cell culture cells treated with both palmitate and TNFa. Together, our study introduces a method to simultaneously measure and quantitatively compare nuclear protein expression patterns in primary adipose tissue and adipocyte cell cultures, which we show can reveal relationships between differentiation and disease states of different adipocyte tissue types.
View details for DOI 10.1194/jlr.D056317
View details for Web of Science ID 000353767200012
View details for PubMedID 25840986