Molecular mechanism of obesity-induced adipose tissue inflammation; the role of Mincle in adipose tissue fibrosis and ectopic lipid accumulation.

Abstract

Metabolic syndrome is a common metabolic disorder that involves multiple organs and is predominantly influenced by obesity, especially the accumulation of visceral fat. It is also known that macrophages that infiltrate obese adipose tissue play an important role in inflammation of the adipose tissue. Macrophage-inducible C-type lectin (Mincle), a new inflammatory regulator found in obese adipose tissue, is expressed in pro-inflammatory M1 macrophages in adipose tissue. In addition, Mincle is expressed in macrophages that form a crown-like structure, where dead or dying adipocytes are surrounded by pro-inflammatory M1 macrophages; within this crown-like structure, adipocyte-macrophage crosstalk may occur in close proximity. Although there is no significant difference in body weight between Mincle-deficient and wild-type mice under high-fat diet, the epididymal fat weight is significantly higher and the liver weight is significantly lower in Mincle-deficient mice than those in wild-type mice. It has been shown that adipose tissue inflammation and fibrosis are attenuated in Mincle-deficient mice when compared with wild-type mice. In addition, Mincle-deficient mice have reduced hepatic lipid accumulation and better glucose metabolism. These results suggest that Mincle signaling in adipose tissue macrophages activates adipose tissue fibroblasts, which leads to adipose tissue fibrosis.