Myeloid-specific deletion of thrombospondin 1 protects against inflammation and insulin resistance in long-term diet-induced obese male mice

摘要

Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. Recent studies demonstrate that TSP1 is highly expressed in adipose tissue (AT) and positively associated with AT inflammation and insulin resistance (IR). In this study, the contribution of different cellular sources of TSP1 to obesity-induced metabolic complications is determined by using mice with either adipocyte or myeloid/mac-rophage-specific deletion of TSP1 in a diet-induced obese model. The results demonstrated that neither adipocyte nor myeloid/macrophage-speciflc deletion of TSPI affected the development of long-term high-fat diet-induced obesity. Adipocyte-specific deletion of TSPI did not protect mice from obesity-induced inflammation and IR. On the contrary, obese mice with myeloid/macrophage loss of TSPI had reduced macrophage accumulation in AT, which was accompanied with reduced inflammation and improved glucose tolerance and insulin sensitivity compared with obese control mice.