SPARC-null mice exhibit increased adiposity without significant differences in overall body weight

Abstract

Secreted protein acidic and rich in cysteine͞osteonectin͞BM-40 (SPARC) is a matrix-associated protein that elicits changes in cell shape, inhibits cell-cycle progression, and influences the synthesis of extracellular matrix (ECM). The absence of SPARC in mice gives rise to aberrations in the structure and composition of the ECM that result in generation of cataracts, development of severe osteopenia, and accelerated closure of dermal wounds. In this report we show that SPARC-null mice have greater deposits of s.c. fat and larger epididymal fat pads in comparison with wild-type mice. Similar to earlier studies of SPARC-null dermis, we observed a reduction in collagen I in SPARC-null fat pads in comparison with wild-type. Although elevated levels of serum leptin were observed in SPARC-null mice, their overall body weights were not significantly different from those of wild-type counterparts. The diameters of adipocytes from SPARC-null versus wild-type epididymal fat pads were 252 ؎ 61 and 161 ؎ 33 m (means ؎ SD), respectively, and there was an increase in adipocyte number within SPARC-null fat pads in comparison with wild-type pads. Thus the absence of SPARC appears to result in an increase in the size of individual adipocytes as well as an increase in the number of adipocytes per fat pad. In fat pads isolated from wild-type mice, SPARC mRNA was associated with both the stromal͞vascular and adipocyte fractions. We propose that SPARC limits the accumulation of adipose tissue in mice in part through its demonstrated effects on the regulation of cell shape and production of ECM.

New insights into elastic fiber assembly

“…All of the phenotypes show variable penetrance with the exception of the bleeding diathesis, which is completely penetrant in all backgrounds, including C57Bl/6. The phenotypes observed in the BSw mfap22/2 mouse are similar to matricellular proteins that bind matrix proteins, but do not contribute to the structural integrity of the ECM, such as thrombospondin (Kyriakides et al, 1998) and secreted protein acidic and rich in cysteine (SPARC) (osteonectin) (Bradshaw et al, 2003).…”

Elevated plasma levels of SPARC in patients with newly diagnosed type 2 diabetes mellitus

“…As a multifunctional glycoprotein binding calcium, collagen and hydroxyapatite (3), SPARC is an extracellular regulatory macromolecule involved in osteogenesis, angiogenesis, wound healing, tumorigenesis, hepatic and renal fibrosis (4)(5)(6). Evidence suggests that a higher level of SPARC appears to inhibit the expansion of abdominal subcutaneous adipose tissue (7), probably by increasing ectopic lipid stores in other tissues such as liver or skeletal muscle resulting in predisposition to insulin resistance (IR). Expression of SPARC is markedly elevated in the adipose tissue in both obese (OB) mice and human individuals (2,8), and is positively regulated by weight change, calorie intake, insulin, and leptin.…”

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

“…SPARC is a multifunctional protein that regulates extracellular matrix (ECM) organization and cell-ECM interactions, leading to the modulation of cell adhesion and migration, promotion of cell survival, and inhibition of cell proliferation (Brekken and Sage, 2000). SPARC null mice have a subtle pheno-type that includes osteopenia (Delany et al, 2000), abnormal dermal collagen fibrils (Bradshaw et al, 2003b), cataractogenesis (Yan et al, 2002), and adiposity (Bradshaw et al, 2003a), and is exacerbated by challenge, including impaired wound healing (Basu et al, 2001;Bradshaw et al, 2002), and an impaired immune response (Kelly et al, 2007;Rempel et al, 2007).…”