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

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.

• Authors: Miyako Tanaka, Kenji Ikeda, Takayoshi Suganami, Chikara Komiya, Kozue Ochi, Ibuki Shirakawa, Miho Hamaguchi, Satoshi Nishimura, Ichiro Manabe, Takahisa Matsuda, Kumi Kimura, Hiroshi Inoue, Yutaka Inagaki, Seiichiro Aoe, Sho Yamasaki, Yoshihiro Ogawa
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 4982 (Sep 19 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 25236782 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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