Group X phospholipase A2 links colonic lipid homeostasis to systemic metabolism via host-microbiota interaction
Hiroyasu Sato,
Yoshitaka Taketomi,
Remi Murase,
Jonguk Park,
Koji Hosomi,
Takayuki Jujo Sanada,
Kenji Mizuguchi,
Makoto Arita,
Jun Kunisawa,
Makoto Murakami
Affiliations
Hiroyasu Sato
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
Yoshitaka Taketomi
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
Remi Murase
Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, School of Pharmacy, Showa University, Tokyo 142-8555, Japan
Jonguk Park
Laboratory of Bioinformatics, Artificial Intelligence Center for Health and Biomedical Research, Osaka 567-0085, Japan
Koji Hosomi
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
Takayuki Jujo Sanada
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
Kenji Mizuguchi
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
Makoto Arita
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
Jun Kunisawa
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
Makoto Murakami
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; Corresponding author
Summary: The gut microbiota influences physiological functions of the host, ranging from the maintenance of local gut homeostasis to systemic immunity and metabolism. Secreted phospholipase A2 group X (sPLA2-X) is abundantly expressed in colonic epithelial cells but is barely detectable in metabolic and immune tissues. Despite this distribution, sPLA2-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 sPLA2-X orchestrates ω3 PUFA-SCFA interplay via modulation of the gut microbiota, thereby secondarily affecting systemic metabolism.
