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Inokuchi JI, Kanoh H, Inamori KI, et al. Homeostatic and pathogenic roles of the GM3 ganglioside. FEBS J. 2021;doi: 10.1111/febs.16076.
Inokuchi, J. I., Kanoh, H., Inamori, K. I., Nagafuku, M., Nitta, T., & Fukase, K. (2021). Homeostatic and pathogenic roles of the GM3 ganglioside. The FEBS journal, . https://doi.org/10.1111/febs.16076
Inokuchi, Jin-Ichi, et al. "Homeostatic and pathogenic roles of the GM3 ganglioside." The FEBS journal vol. (2021). doi: https://doi.org/10.1111/febs.16076
Inokuchi JI, Kanoh H, Inamori KI, Nagafuku M, Nitta T, Fukase K. Homeostatic and pathogenic roles of the GM3 ganglioside. FEBS J. 2021 Jun 14; doi: 10.1111/febs.16076. Epub 2021 Jun 14. PMID: 34125497.
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FEBS J. 2021 Jun 14; doi: 10.1111/febs.16076. Epub 2021 Jun 14.

Homeostatic and pathogenic roles of the GM3 ganglioside.

The FEBS journal

Jin-Ichi Inokuchi, Hirotaka Kanoh, Kei-Ichiro Inamori, Masakazu Nagafuku, Takahiro Nitta, Koichi Fukase

Affiliations

  1. Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  2. Core for Medicine and Science Collaborative Research and Education (MS-CORE), Project Research Center for Fundamental Sciences, Osaka University, Japan.
  3. Department of Chemistry, Graduate School of Science, Osaka University, Japan.

PMID: 34125497 DOI: 10.1111/febs.16076

Abstract

Two decades ago, we achieved molecular cloning of ganglioside GM3 synthase (GM3S; ST3GAL5), the enzyme responsible for initiating biosynthesis of complex gangliosides. The efforts of our research group since then have been focused on clarifying the physiological and pathological roles of gangliosides, particularly GM3. This review summarizes our long-term studies on the roles of GM3 in insulin resistance and adipogenesis in adipose tissues, cholesterol uptake in intestine, and leptin resistance in hypothalamus. We hypothesized that GM3 plays a role in innate immune function of macrophages and demonstrated that molecular species of GM3 with differing acyl-chain structures and modifications functioned as pro- and anti-inflammatory endogenous Toll-like receptor 4 (TLR4) modulators in macrophages. Very-long-chain and α-hydroxy GM3 species enhanced TLR4 activation, whereas long-chain and unsaturated GM3 species counteracted this effect. Lipidomic analyses of serum and adipose tissues revealed that imbalances between such pro- and anti-inflammatory GM3 species promoted progression of metabolic disorders. GM3 thus functions as a physiological regulatory factor controlling the balance between homeostatic and pathological states. Ongoing studies based on these findings will clarify the mechanisms underlying ganglioside-dependent control of energy homeostasis and innate immune responses.

© 2021 Federation of European Biochemical Societies.

Keywords: GM3 ganglioside; NPC1L1; TLR4; adipocytes; cholesterol transport; chronic inflammation; innate immunity; insulin resistance; leptin resistance; metabolic syndrome; obesity

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