Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis

Nat Commun. 2014 Sep 19;5:4982. doi: 10.1038/ncomms5982.

Abstract

In obesity, a paracrine loop between adipocytes and macrophages augments chronic inflammation of adipose tissue, thereby inducing systemic insulin resistance and ectopic lipid accumulation. Obese adipose tissue contains a unique histological structure termed crown-like structure (CLS), where adipocyte-macrophage crosstalk is known to occur in close proximity. Here we show that Macrophage-inducible C-type lectin (Mincle), a pathogen sensor for Mycobacterium tuberculosis, is localized to macrophages in CLS, the number of which correlates with the extent of interstitial fibrosis. Mincle induces obesity-induced adipose tissue fibrosis, thereby leading to steatosis and insulin resistance in liver. We further show that Mincle in macrophages is crucial for CLS formation, expression of fibrosis-related genes and myofibroblast activation. This study indicates that Mincle, when activated by an endogenous ligand released from dying adipocytes, is involved in adipose tissue remodelling, thereby suggesting that sustained interactions between adipocytes and macrophages within CLS could be a therapeutic target for obesity-induced ectopic lipid accumulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipose Tissue / metabolism
  • Adipose Tissue / physiopathology*
  • Animals
  • Fibrosis
  • Inflammation / metabolism
  • Insulin Resistance
  • Lectins, C-Type / metabolism*
  • Ligands
  • Lipids / chemistry
  • Liver / metabolism
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled

Substances

  • Adgre1 protein, mouse
  • Clecsf8 protein, mouse
  • Lectins, C-Type
  • Ligands
  • Lipids
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled

Associated data

  • GEO/GSE52338