SPARC: a key player in the pathologies associated with obesity and diabetes

Abstract

SPARC (secreted protein acidic and rich in cysteine, also known as osteonectin or BM-40) is a widely expressed profibrotic protein with pleiotropic roles, which have been studied in a variety of conditions. Notably, SPARC is linked to human obesity; SPARC derived from adipose tissue is associated with insulin resistance and secretion of SPARC by adipose tissue is increased by insulin and the adipokine leptin. Furthermore, SPARC is associated with diabetes complications such as diabetic retinopathy and nephropathy, conditions that are ameliorated in the Sparc-knockout mouse model. As a regulator of the extracellular matrix, SPARC also contributes to adipose-tissue fibrosis. Evidence suggests that adipose tissue becomes increasingly fibrotic in obesity. Fibrosis of subcutaneous adipose tissue may restrict accumulation of triglycerides in this type of tissue. These triglycerides are, therefore, diverted and deposited as ectopic lipids in other tissues such as the liver or as intramyocellular lipids in skeletal muscle, which predisposes to insulin resistance. Hence, SPARC may represent a novel and important link between obesity and diabetes mellitus. This Review is focused on whether SPARC could be a key player in the pathology of obesity and its related metabolic complications.

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

“…Furthermore, SPARC levels were found to correlate positively with BMI, FAT%, TG, f-INS, 2hINS, and HOMA IR in simple regression analysis, and multiple regression analysis showed that TG and HOMA IR were independently correlated with plasma SPARC levels. As shown in the literature, SPARC has been shown to inhibit the differentiation of preadipocytes to mature adipocytes, and to increase adipose tissue fibrosis (15,16). Thus, SPARC could inhibit the expansion of subcutaneous abdominal adipose tissue (6), reduce the ability of adipose tissue to store TGs, and increase the TGs in the circulation and lipid infiltration of other organs resulting in IR.…”

SPARC Oppositely Regulates Inflammation and Fibrosis in Bleomycin-Induced Lung Damage

“…The matricellular glycoprotein termed secreted protein acidic and rich in cysteine (SPARC) has a key role in extracellular matrix (ECM) assembly and molding. Consistently, SPARC has been implicated in the pathogenesis of several fibrotic disorders, such as adipose tissue fibrosis, 1 hepatic fibrosis, 2,3 lung fibrosis, 4 and scleroderma. 5 This notion comes from data generated in Sparc Ϫ/Ϫ mice or gene-silencing strategies in models of skin, liver, and pulmonary fibrosis.…”

Osteonectin (SPARC) Expression in Vascular Calcification: In Vitro and Ex Vivo Studies

“…In fact, osteonectin is associated with diabetes complications such as diabetic retinopathy and nephropathy, conditions that are ameliorated in the SPARC-knockout mouse model and, as a regulator of the extracellular matrix, osteonectin also contributes to adipose-tissue fibrosis. [18]. Regarding tumors, osteonectin modulate the interaction between tumor cells and the normal surrounding cells, affecting proliferation, survival and migration of cancer cells, tumor invasion, and metastasis [7].…”