Group X phospholipase A 2 links colonic lipid homeostasis to systemic metabolism via host-microbiota interaction.

Autor: Sato H; Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan., Taketomi Y; Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan., Murase R; Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, School of Pharmacy, Showa University, Tokyo 142-8555, Japan., Park J; Laboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, Osaka 567-0085, Japan., Hosomi K; Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan., Sanada TJ; Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan., Mizuguchi K; Laboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, Osaka 567-0085, Japan; Institute for Protein Research, Osaka University, Osaka 565-0871, Japan., Arita M; Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan; Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan., Kunisawa J; Laboratory of Vaccine Materials and Laboratory of Gut Environmental System, Microbial Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan., Murakami M; Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan. Electronic address: makmurak@m.u-tokyo.ac.jp.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2024 Oct 22; Vol. 43 (10), pp. 114752. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1016/j.celrep.2024.114752
Abstrakt: The gut microbiota influences physiological functions of the host, ranging from the maintenance of local gut homeostasis to systemic immunity and metabolism. Secreted phospholipase A 2 group X (sPLA 2 -X) is abundantly expressed in colonic epithelial cells but is barely detectable in metabolic and immune tissues. Despite this distribution, sPLA 2 -X-deficient (Pla2g10 -/- ) mice displayed variable obesity-related phenotypes that were abrogated after treatment with antibiotics or cohousing with Pla2g10 +/+ mice, suggesting the involvement of the gut microbiota. Under housing conditions where Pla2g10 -/- mice showed aggravation of diet-induced obesity and insulin resistance, they displayed increased colonic inflammation and epithelial damage, reduced production of polyunsaturated fatty acids (PUFAs) and lysophospholipids, decreased abundance of several Clostridium species, and reduced levels of short-chain fatty acids (SCFAs). These obesity-related phenotypes in Pla2g10 -/- mice were reversed by dietary supplementation with ω3 PUFAs or SCFAs. Thus, colonic sPLA 2 -X orchestrates ω3 PUFA-SCFA interplay via modulation of the gut microbiota, thereby secondarily affecting systemic metabolism.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE