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

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

Author information

1
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
2
1] Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan [2] Japan Science and Technology Agency, PRESTO, Tokyo, Japan.
3
Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
4
1] Department of Cardiovascular Medicine, The University of Tokyo, Tokyo 113-8655, Japan [2] Translational Systems Biology and Medicine Initiative, The University of Tokyo, Tokyo 113-8655, Japan [3] Jichi Medical University, Tochigi 329-0498, Japan.
5
Department of Cardiovascular Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
6
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Fujisawa 251-8555, Japan.
7
Department of Physiology and Metabolism, Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa 920-8641, Japan.
8
Department of Regenerative Medicine, Center for Matrix Biology and Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan.
9
Department of Home Economics, Otsuma Women's University, Tokyo 102-8357, Japan.
10
Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.

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.

PMID:
25236782
DOI:
10.1038/ncomms5982
[Indexed for MEDLINE]

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