Journal
ADIPOCYTE
Volume 3, Issue 1, Pages 81-84Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/adip.26990
Keywords
matricellular protein; obesity; diabetes; adipocyte; myocardium; extracellular matrix; angiogenesis; inflammation; transforming growth factor-beta
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Funding
- NIH [R01 HL76246, R01 HL85440]
- Wilf Family Cardiovascular Research Institute
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Matricellular proteins are extracellular macromolecules that do not serve a structural role, but when incorporated into the matrix, modulate cell: cell and cell: matrix interactions. The matricellular protein thrombospondin (TSP)-1, a potent angiostatic mediator and activator of transforming growth factor (TGF)-beta, is upregulated in diabetes and obesity and may be involved in the pathogenesis of metabolic dysregulation and organ dysfunction. This manuscript discusses recently published observations on the role of TSP-1 in metabolic disease. In obesity models induced by a high-fat diet, adipose tissue TSP-1 upregulation induces inflammation and promotes weight gain and metabolic dysfunction. TSP-1 may have direct effects on adipocyte proliferation and fatty acid uptake. In diabetic subjects, TSP-1 upregulation in kidney, myocardium, and vascular tissue may promote dysfunction. In the myocardium, TSP-1 upregulation may transduce angiostatic signals inducing vascular rarefaction. Dissection of the functional domains involved in TSP-1 actions may lead to the development of peptide-based strategies for treatment of diabetes and its complications.
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