Abstract

Objective: The matricellular Secreted-Protein, Acidic and Rich-in-Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose-tissue (AT) collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human AT is influenced by glucose metabolism and adipokines.

Research Design and Methods: Serum and AT-biopsies were obtained from morbidly obese non-diabetic subjects undergoing bariatric surgery and lean controls for analysis of metabolic markers, SPARC and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet (VLCD) of 1883kJ (450kcal)/day for 16 weeks and serial subcutaneous-abdominal-AT (SCAT) biopsies (weight loss:28±3.7kg). Another 6 lean subjects underwent fast food-based hyperalimentation for 4 weeks (weight gain:7.2±1.6 kg). Finally, visceral-AT (VAT)-explants were cultured with recombinant leptin, insulin and glucose, and SPARC mRNA and protein-expression determined by western-blot analyses.

Results: SPARC expression in human AT correlated with fat-mass and was higher in SCAT. Weight loss induced by VLCD lowered SPARC expression by 33% and increased by 30% in AT of subjects gaining weight after fast-food diet. SPARC expression was correlated with leptin independent of fat-mass and correlated with HOMA-IR. In-vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in VAT explants while glucose decreased SPARC protein.

Conclusions: Our data suggests that SPARC expression is predominant in subcutaneous fat and its expression and secretion in AT are influenced by fat mass, leptin, insulin and glucose. The pro-fibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.