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Homeostatic and pathogenic roles of GM3 ganglioside molecular species in TLR4 signaling in obesity.
Kanoh, Hirotaka; Nitta, Takahiro; Go, Shinji; Inamori, Kei-Ichiro; Veillon, Lucas; Nihei, Wataru; Fujii, Mayu; Kabayama, Kazuya; Shimoyama, Atsushi; Fukase, Koichi; Ohto, Umeharu; Shimizu, Toshiyuki; Watanabe, Taku; Shindo, Hiroki; Aoki, Sorama; Sato, Kenichi; Nagasaki, Mika; Yatomi, Yutaka; Komura, Naoko; Ando, Hiromune; Ishida, Hideharu; Kiso, Makoto; Natori, Yoshihiro; Yoshimura, Yuichi; Zonca, Asia; Cattaneo, Anna; Letizia, Marilena; Ciampa, Maria; Mauri, Laura; Prinetti, Alessandro; Sonnino, Sandro; Suzuki, Akemi; Inokuchi, Jin-Ichi.
Afiliação
  • Kanoh H; Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Nitta T; Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Go S; Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Inamori KI; Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Veillon L; Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Nihei W; Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Fujii M; Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan.
  • Kabayama K; Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan.
  • Shimoyama A; Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan.
  • Fukase K; Department of Chemistry, Graduate School of Science, Osaka University, Osaka, Japan.
  • Ohto U; Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
  • Shimizu T; Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
  • Watanabe T; Medical and Pharmaceutical Information Science, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Shindo H; Medical and Pharmaceutical Information Science, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Aoki S; Medical and Pharmaceutical Information Science, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Sato K; Medical and Pharmaceutical Information Science, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Nagasaki M; Department of Cardiovascular Medicine and Computational Diagnostic Radiology & Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Yatomi Y; Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Komura N; Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN), Gifu University, Gifu, Japan.
  • Ando H; Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN), Gifu University, Gifu, Japan.
  • Ishida H; Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN), Gifu University, Gifu, Japan.
  • Kiso M; Department of Applied Bio-organic Chemistry, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan.
  • Natori Y; Organization for Research and Community Development, Gifu University, Gifu, Japan.
  • Yoshimura Y; Division of Organic and Pharmaceutical Chemistry, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Zonca A; Division of Organic and Pharmaceutical Chemistry, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Cattaneo A; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
  • Letizia M; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
  • Ciampa M; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
  • Mauri L; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
  • Prinetti A; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
  • Sonnino S; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
  • Suzuki A; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy.
  • Inokuchi JI; Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
EMBO J ; 39(12): e101732, 2020 06 17.
Article em En | MEDLINE | ID: mdl-32378734
Innate immune signaling via TLR4 plays critical roles in pathogenesis of metabolic disorders, but the contribution of different lipid species to metabolic disorders and inflammatory diseases is less clear. GM3 ganglioside in human serum is composed of a variety of fatty acids, including long-chain (LCFA) and very-long-chain (VLCFA). Analysis of circulating levels of human serum GM3 species from patients at different stages of insulin resistance and chronic inflammation reveals that levels of VLCFA-GM3 increase significantly in metabolic disorders, while LCFA-GM3 serum levels decrease. Specific GM3 species also correlates with disease symptoms. VLCFA-GM3 levels increase in the adipose tissue of obese mice, and this is blocked in TLR4-mutant mice. In cultured monocytes, GM3 by itself has no effect on TLR4 activation; however, VLCFA-GM3 synergistically and selectively enhances TLR4 activation by LPS/HMGB1, while LCFA-GM3 and unsaturated VLCFA-GM3 suppresses TLR4 activation. GM3 interacts with the extracellular region of TLR4/MD2 complex to modulate dimerization/oligomerization. Ligand-molecular docking analysis supports that VLCFA-GM3 and LCFA-GM3 act as agonist and antagonist of TLR4 activity, respectively, by differentially binding to the hydrophobic pocket of MD2. Our findings suggest that VLCFA-GM3 is a risk factor for TLR4-mediated disease progression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monócitos / Transdução de Sinais / Receptor 4 Toll-Like / Gangliosídeo G(M3) / Obesidade Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: EMBO J Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monócitos / Transdução de Sinais / Receptor 4 Toll-Like / Gangliosídeo G(M3) / Obesidade Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: EMBO J Ano de publicação: 2020 Tipo de documento: Article