Dynamic changes in extracellular matrix gene regulation in adipose tissue and impact on preadipocyte proliferation and apoptosis

Adipose expansion occurs by hypertrophy and hyperplasia which may be influenced by the extracellular matrix (ECM). In the current study, we observed adipose depot specific changes in ECM expression under diet induced obesity. We examined ECM transcript and protein levels in C57BL/6 mice fed a control or high fat diet for 4, 8, and 12 weeks. We report that the transcript levels of collagen1A1, collagen VI, and biglycan display increased expression in the high fat diet mice that shifts from the subcutaneous adipose to the epididymal adipose over time. Protein levels of collagen1A1 and collagen VI do not correlate with transcript levels. We saw changes in the expression of MMPs 3 and 13 (P < 0.05) in mice fed a high fat diet, suggesting that ECM degradation by MMPs may be a reason for the disparity between protein and transcript levels. This study indicates that ECM genes are differentially regulated in different depots. Also, transcripts and proteins of the ECM may not correlate in obesity, perhaps due to degradation by MMPs. In a separate study, we treated preadipocytes with biglycan, decorin and fibronectin to evaluate their effects on preadipocyte proliferation. Decorin and biglycan caused a significant reduction of preadipocyte proliferation (P < 0.05), while fibronectin stimulated preadipocyte proliferation (P < 0.05). Thus, we provide evidence that ECM genes may directly regulate preadipocyte proliferation. Grant Funding Source: Purdue University