Alterations in adipose tissue (AT) extracellular matrix (ECM) organization and/or composition accompany several pathologies, including obesity and diabetes. The need to better understand overall AT ECM composition and structure is essential to unraveling the pathogenesis of obesity, especially when considering that a given tissue ‘matrisome’ (a protein signature comprised of core ECM proteins plus ECM-associated proteins) can consist of several hundred proteins. Recent methods have exploited the insolubility of ECM proteins to allow their enrichment from decellularized tissues and subsequent proteomic analysis, but to our knowledge these methods have not been performed in AT. In this study, we used this methodology to characterize the AT matrisome in female mice fed control or high-fat diets. Female C57BL/6J mice were fed control (n=6) or high-fat (n=6) diets for 8 weeks. Body weights were obtained weekly and body composition was analyzed biweekly via NMR. At study end, AT samples were decellularized and enriched for ECM proteins using a commercially available kit. The ECM-enriched fractions were digested, deglycosylated, fractionated into peptides, LC-MS/MS performed, and raw data analyzed using Proteome Discoverer v2.2. Our data reveal that high-fat feeding does not significantly affect AT collagen levels in female mice, but does significantly increase glycoprotein levels (spondin 1, SPARC, adiponectin). Conversely, a significant decrease in the proteoglycan, PRG3, was also observed in AT with high-fat feeding. Several additional ECM-associated proteins, which have undefined roles AT, were differentially regulated by high-fat diet feeding in female mice. Current studies are focused on determining how these proteins influence AT metabolism.
J.L. Bailey: None. C.M. Elks: None.
National Institutes of Health