Small leucine-rich proteoglycans and their role in adipose tissue

During obesity, adipose tissue expands in response to increased energy storage. One of the physiological changes that occur during adipose tissue expansion is extracellular matrix (ECM) remodeling. The contents of this dissertation describe three studies that examine the expression of ECM proteins in obese mice and the impact of small leucine-rich proteoglycans (SLRPs) on adipose tissue function. In the first study, the expression of ECM proteins was measured in the epididymal and subcutaneous adipose tissue of mice fed a low fat or high fat diet over time (4, 8, and 12 weeks of dietary intervention). The results of this study indicate that the gene expression pattern of some ECM proteins is adipose depot specific. In a second study, 3T3-L1 preadipocytes were plated on cell culture dishes coated with biglycan and decorin. Treatment with biglycan and decorin resulted in significantly decreased preadipocyte cell number. It was further demonstrated that biglycan and decorin increased apoptosis in 3T3-L1 preadipocytes. The third study examines the effect of biglycan absence on adipose tissue function using whole-body biglycan knockout mice. Biglycan knockout mice had decreased expression of epididymal adipose tissue IL-6 transcript along with increased circulating levels of adiponectin. However, siRNA knockdown of biglycan in 3T3-L1 adipocytes yielded lower levels of adiponectin. Differences in extracellular environments could explain the discrepancy in results observed in the in vivo and in vitro systems. In summary, the studies contained in this document indicate a possible role for SLRPs in adipose tissue formation, function and inflammation