Journal of Glycobiology
Open Access

Thrombospondin1, an important mediator of obesity-associated inflammation and insulin resistance

Glycobiology World Congress

August 10-12, 2015 Philadelphia, USA

Shuxia Wang

Posters-Accepted Abstracts: J Glycobiol

Abstract :

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 chemo attractant
and pro inflammatory activator for macrophages in inflamed AT and promotes obesity-induced inflammation and IR.