Abstract
Expression of the gene encoding TSP1, an endogenous anti-angiogenic factor, was quantified in subcutaneous adipose tissue of non-diabetic subjects with normal (NGT) or impaired glucose tolerance (IGT), covering a wide range of BMI (19–55 Kg/m2) and insulin sensitivity (SI =1.02–26.77 x 10−5x min−1/pM). TSP1 mRNA was significantly higher in the adipocyte compared to the stromal vascular fraction of adipose tissue biopsies, suggesting that TSP1 is a true adipokine. TSP1 mRNA demonstrated a significant positive association with BMI, and a significant negative association with SI. TSP1 correlated positively with markers of inflammation, including CD68 and MCP1, and the relationship with inflammatory markers remained significant on controlling for BMI and SI. Pioglitazone (but not metformin) treatment resulted in a significant 54% decrease in adipose TSP1 gene expression. In in vitro experiments, adipocytes co-cultured with macrophages demonstrated elevated TSP1 gene expression. Thus, TSP1 is an adipokine that is highly expressed in obese, insulin resistant subjects which is increased with adipose inflammation, and is decreased by pioglitazone. Further experiments will dissect mechanisms underlying the effects of pioglitazone on TSP-1 gene expression and delineate the role of TSP1 in linking macrophage-driven inflammation and altered adipocyte function in metabolic syndrome.
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