Proteomic characterization of thiazolidinedione regulation of obese adipose secretome in Zucker obese rats

Signaling molecules released by adipose tissue have been implicated in inflammation, adipocyte dysfunction and systemic insulin resistance. In this study, we used 2-D LC-MS/MS and quantitative proteomics approaches to characterize the obese adipose secretory proteins that are responsive to the thiazolidinediones class of PPAR-γ agonizts. We first showed the differential secretion profiling between obese and lean adipose tissue; 87 proteins were detected from the conditioned medium of adipose tissue of Zucker obese rats compared with 31 from lean rats. A total of 57 proteins comprising immune factors, inflammatory molecules, collagens, proteases, and extracellular matrix proteins were detected from obese, but not lean adipose tissue. More importantly, a quantitative proteomics approach using ¹⁸O proteolytic labeling allowed quantification of the difference in the secretion levels of 77 proteins, and thiazolidinediones treatment suppressed the secretion of most of the obese adipose tissue secretome, thus resembling a lean tissue. We have demonstrated an application of identifying the obese adipose secretome and characterizing the regulation of adipose secretion in obesity and insulin resistance. Our data provide the first evidence of changes in adipose secretion in obesity at a global level and show that such changes are correlated with systemic insulin resistance.