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

Nature Reviews Endocrinology volume 6, pages 225–235 (2010)Cite this article

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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.

Key Points

  • An increase in the levels of SPARC is found in animals and human individuals with obesity and insulin resistance

  • Raised SPARC concentrations are associated with the development of diabetes-associated complications

  • SPARC is involved in strengthening bone but raised concentrations of the protein are associated with increased cardiovascular risk

  • Associations between SPARC and cancer have been postulated, but the exact role of this protein in tumorigenesis is unclear

  • SPARC antagonism may help in the prevention of obesity-related complications

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Figure 1: Structure and functional properties of SPARC.
Figure 2: Regulation of adipose mass by SPARC and leptin.

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Authors and Affiliations

  1. Department of Diabetes and Vascular Medicine, Peninsula College of Medicine and Dentistry, University of Exeter, Peninsula Medical School Building, Barrack Road, Exeter, EX2 5DW, UK

    Katarina Kos

  2. Diabetes and Endocrinology Clinical Research Unit, Clinical Sciences Center, University Hospital Aintree, Longmoor Lane, L9 7AL, Liverpool, UK

    John P. H. Wilding

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  1. Katarina Kos
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  2. John P. H. Wilding
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Correspondence to Katarina Kos.

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Kos, K., Wilding, J. SPARC: a key player in the pathologies associated with obesity and diabetes. Nat Rev Endocrinol 6, 225–235 (2010). https://doi.org/10.1038/nrendo.2010.18

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