Shuxia Wang
University of Kentucky, USA
Posters-Accepted Abstracts: J Diabetes Metab
Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. It is highly expressed in visceral fat tissue (AT) from obese and insulin resistant humans or obese rodents. Recently, both human and rodent data from our lab and others suggest that TSP1 plays an important role in obesity-associated chronic inflammation and insulin resistance (IR). The positive association of adipose tissue TSP1 with AT inflammation and IR has been observed in obese human subjects. By using global TSP1 deficient mice, we revealed a novel role for TSP1 in stimulating macrophage accumulation and activation in AT that promotes inflammation and IR resulting from high fat diet-induced obesity (DIO). Specifically, we found that feeding a high fat diet to wild type and TSP1 deficient mice for 16 weeks caused similar obesity, but only mice with TSP1 deficiency remained insulin-sensitive. The protection of TSP1 deficient mice against IR was associated with reduced ATMs, decreased adipose and systemic inflammation, and reduced AT fibrosis. Moreover, TSP1 deficiency protected mice from obesity-induced hypertension and kidney damage. In vitro data demonstrated that TSP1 deficient monocyte/macrophages had decreased chemotactic activity and a reduced pro-inflammatory phenotype. TSP1 treatment stimulated macrophage migration. In addition, TSP1 stimulated macrophages to produce pro-inflammatory cytokines, which required TLR4 activation and was mediated by interaction between the type 1 repeats of TSP1 (TSR) and its receptor-CD36. Collectively, these data suggest that TSP1 acts as both a chemoattractant and proinflammatory activator for macrophages in inflamed AT, and promotes obesity-induced inflammation and IR.
Email: swang7@email.uky.edu
