TY - JOUR
T1 - Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis
AU - Tanaka, Miyako
AU - Ikeda, Kenji
AU - Suganami, Takayoshi
AU - Komiya, Chikara
AU - Ochi, Kozue
AU - Shirakawa, Ibuki
AU - Hamaguchi, Miho
AU - Nishimura, Satoshi
AU - Manabe, Ichiro
AU - Matsuda, Takahisa
AU - Kimura, Kumi
AU - Inoue, Hiroshi
AU - Inagaki, Yutaka
AU - Aoe, Seiichiro
AU - Yamasaki, Sho
AU - Ogawa, Yoshihiro
N1 - Funding Information:
We thank Drs Shizuo Akira and Masaru Okabe, Osaka University, for the generous gift of Mincle KO mice and Egfp Tg mice, respectively, and Dr Takahisa Nakamura, Cincinnati Children’s Hospital Medical Center, for critical reading of the manuscript. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Ministry of Health, Labour and Welfare of Japan, and Japan Science and Technology Agency, PRESTO. This work was also supported by research grants from Takeda Medical Research Foundation, The Tokyo Biochemical Research Foundation, Astellas Foundation for Research on Metabolic Disorders, The Mochida Memorial Foundation for Medical and Pharmaceutical Research and The Ichiro Kanehara Foundation.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms5982
DO - 10.1038/ncomms5982
M3 - Article
C2 - 25236782
AN - SCOPUS:84923367724
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 4982
ER -
