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, and 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 remodeling, thereby suggesting that sustained interactions between adipocytes and macrophages within CLS could be a therapeutic target for obesity-induced ectopic lipid accumulation.
Research Area "Elucidation and control of the mechanisms underlying chronic inflammation"
Research Theme "Molecular mechanisms underlying obesity-induced chronic inflammation"
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, and Yoshihiro Ogawa. “Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis”. Nature Communications, Published online September 19, 2014, doi : 10.1038/ncomms5982
Takayoshi Suganami, M.D., Ph.D.
Professor, Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Yoshihiro Ogawa, M.D., Ph.D.
Professor, Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Koji Matsuo, Takafumi Kawaguchi, and Toshiyuki Shingo
Life Innovation Group, Department of Innovation Research, JST