Inactivation of SPARC enhances high-fat diet-induced obesity in mice

Secreted protein, acidic and rich in cysteine (SPARC), a matricellular protein, modulates extracellular matrix assembly and turnover in many physiological processes. SPARC-null mice exhibit an increased accumulation of adipose tissue. To distinguish between the functions of SPARC in adipogenesis during development and adulthood, we studied wild-type (WT) and SPARC-null mice maintained on a normal (low-fat) or high-fat (HF) diet. On an HF diet, SPARC-null mice exhibited significantly greater weight gain, in comparison to their WT counterparts, and had an enhanced cortical bone area that was likely due to increased mechanical loading. Diet-induced obesity (DIO) was also associated with an increase in vertebral trabecular bone in WT mice, but a significant change in this parameter was not observed in SPARC-null animals. We show that SPARC inhibits mitotic clonal expansion of preadipocytes at an early stage of adipogenesis. Moreover, there were substantially diminished levels of type I collagen in SPARC-null ...