The matricellular protein SPARC/osteonectin as a newly identified factor up-regulated in obesity

Alterations in the expression level of genes may contribute to the developm ent and pathophysiology of obesity. To find genes differentially expressed in adipose tissue during obesity, we performed suppression subtractive hybr idization on epididymal fat mRNA from goldthioglucose (GTG) obese mice and from their lean littermates. We identified the secreted protein acidic and rich in cysteine (SPARC), a protein that mediates cell-matrix interactions and plays a role in modulation of cell adhesion, differentiation, and angio genesis. SPARC mRNA expression in adipose tissue was markedly increased (be tween 3- and B fold) in three different models of obesity, i.e, G;TG mice, ob/ob mice, and AKR mice, after 6 weeks of a high fat diet. Immunoblotting of adipocyte extracts revealed a similar increase in protein level, Using a SPARC-specific ELISA, we demonstrated that SPARC is secreted by isolated a dipocytes, We found that insulin administration to mice increased SPARC mRN A in the adipose tissue. Food deprivation had no effect on SPARC expression , but after high fat refeeding SPARC mRNA levels were significantly increas ed. Our results reveal both hormonal and nutritional regulation of SPARC ex pression in the adipocyte, and importantly, its alteration in obesity. Fina lly, we show that purified SPARC increased mRNA levels of plasminogen activ ator inhibitor 1 (PAI-1) in cultured rat adipose tissue suggesting that ele vated adipocyte expression of SPARC might contribute to the abnormal expres sion of PAI-1 observed in obesity, We propose that SPARC is a newly identif ied autocrine/paracrine factor that could affect key functions in adipose t issue physiology and pathology.