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Ghosh, A.R.* ; Bhattacharya, R.* ; Bhattacharya, S.* ; Nargis, T.* ; Rahaman, O.* ; Duttagupta, P.* ; Raychaudhuri, D.* ; Chen Liu, C.S.* ; Roy, S.* ; Ghosh, P.* ; Khanna, S.* ; Chaudhuri, T.* ; Tantia, O.* ; Haak, S. ; Bandyopadhyay, S.* ; Mukhopadhyay, S.* ; Chakrabarti, P.* ; Ganguly, D.*

Adipose recruitment and activation of plasmacytoid dendritic cells fuel metaflammation.

Diabetes 65, 3440-3452 (2016)
Publ. Version/Full Text Postprint DOI
Open Access Green
In obese individuals the visceral adipose tissue (VAT) becomes seat of chronic low grade inflammation (metaflammation). But the mechanistic link between increased adiposity and metaflammation remains largely unclear. We report here that in obese individuals deregulation of a specific adipokine, chemerin, contributes to innate initiation of metaflammation, by recruiting circulating plasmacytoid dendritic cells (pDCs) into visceral adipose tissue via chemokine-like receptor 1 (CMKLR1). Adipose tissue-derived high mobility group B1 (HMGB1) protein, activates toll-like receptor 9 (TLR9) in the adipose-recruited pDCs by transporting extracellular DNA via receptor for advanced glycation endproducts (RAGE) and induces production of type I interferons. Type I interferons in turn help in proinflammatory polarization of adipose-resident macrophages. Interferon signature gene expression in VAT correlates with both adipose tissue and systemic insulin resistance in obese individuals, represented by ADIPO-IR and HOMA2-IR respectively, and defines two subgroups with different susceptibility to insulin resistance. Thus our study reveals a hitherto unknown pathway that drives adipose tissue inflammation and consequent insulin resistance in obesity.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Systemic-lupus-erythematosus; Alpha Monoclonal-antibody; Diet-induced Obesity; Insulin-resistance; Viral-infection; Nk Cells; Cpg-oligodeoxynucleotides; Macrophage Polarization; Antimicrobial Peptide; Tissue Macrophages
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 65, Issue: 11, Pages: 3440-3452 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed