Abstract
Low-grade inflammation (LGI) is a central phenomenon in the genesis of obesity and insulin-resistance characterized by IL-6 in human serum. Whereas this LGI was initially thought to be mainly attributed to macrophage activation, it is now known that pre-adipocytes and adipocytes secrete several adipokines including IL-6 and participate to LGI and associated pathologies. In macrophages, HMGB1 is a nuclear yet secreted protein and acts as a cytokine to drive the production of inflammatory molecules through RAGE and TLR2/4. In this paper we tested the secretion of HMGB1 and the auto- and paracrine contribution to fat inflammation using the human preadipocyte cell line SW872 as a model. We showed that 1) human SW872 secreted actively HMGB1, 2) IL-6 production was positively linked to high levels of secreted HMGB1, 3) recombinant HMGB1 boosted IL-6 expression and this effect was mediated by the receptor RAGE and did not involve TLR2 or TLR4. These results suggest that HMGB1 is a major adipokine contributing to LGI implementation and maintenance, and can be considered as a target to develop news therapeutics in LGI associated pathologies such as obesity and type II diabetes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipose Tissue / metabolism
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Adipose Tissue / pathology*
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Blotting, Western
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Cell Proliferation
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Chronic Disease
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Fluorescent Antibody Technique
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HMGB1 Protein / antagonists & inhibitors
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HMGB1 Protein / genetics
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HMGB1 Protein / metabolism*
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Humans
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Inflammation / metabolism
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Inflammation / pathology*
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Interleukin-6 / genetics
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Interleukin-6 / metabolism*
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Liposarcoma / genetics
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Liposarcoma / metabolism*
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Liposarcoma / pathology
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Receptor for Advanced Glycation End Products / genetics
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Receptor for Advanced Glycation End Products / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Toll-Like Receptor 2 / genetics
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Toll-Like Receptor 2 / metabolism
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / metabolism
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Tumor Cells, Cultured
Substances
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HMGB1 Protein
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HMGB1 protein, human
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Interleukin-6
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RNA, Messenger
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RNA, Small Interfering
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Receptor for Advanced Glycation End Products
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Toll-Like Receptor 2
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Toll-Like Receptor 4
Grants and funding
This work was supported by grants from CPER-FEDER GRII, University of La Réunion and the the “Structure Fédérative Environnement, Biodiversité, Santé” University of La La Réunion. BN holds a fellowship from the Biodiversité, Santé” Environnement, Biodiversité, Santé” University of La Réunion. MM and MKG hold fellowships from Regional Council of La Réunion. VGTH is a fellow from the French Ministry (contrat doctoral). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.