Macrophage very low density lipoprotein receptor regulates adipose tissue inflammation in obesity

Abstract

Adipose tissue macrophages (ATMs) are key players to balance pro- and anti-inflammatory responses in fat tissues. In obesity, increased ATMs have been implicated in pro-inflammatory responses and lipid dysregulation. However, underlying mechanisms of lipid accumulation in ATMs of obese animals and their roles are largely unknown. In this study, we demonstrated that elevated expression of very low density lipoprotein receptor (VLDLR) could potentiate adipose tissue inflammation and insulin resistance in obesity. The level of adipose tissue VLDLR in obese animals were elevated, and its expression level was positively correlated with those of pro-inflammatory marker genes. Compared to wild-type mice, VLDLR homozygous-null mice exhibited attenuated insulin resistance and adipose tissue inflammation, concommitantly with less proinflammatory ATMs upon high-fat diet (HFD). In macrophages, the lack of VLDLR prevented lipid uptake and suppressed VLDL-dependent proinflammatory gene expression. Taken together, these data suggest that an elevated macrophage VLDLR expression in obesity would contribute to adipose tissue inflammation via lipid accumulation in ATMs. This work was supported by National Creative Research Initiative Program (2011-0018312) funded by the ministry of Education, Science, and Technology (MEST). K. C. Shin and S. S. Choe were supported by the BK21 program, Korea.