Group X phospholipase A2 links colonic lipid homeostasis to systemic metabolism via host-microbiota interaction

• Published in: Cell reports (Cambridge) Vol. 43; no. 10; p. 114752
• Main Authors: Sato, Hiroyasu, Taketomi, Yoshitaka, Murase, Remi, Park, Jonguk, Hosomi, Koji, Sanada, Takayuki Jujo, Mizuguchi, Kenji, Arita, Makoto, Kunisawa, Jun, Murakami, Makoto
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 22-10-2024; Elsevier
• Subjects: colon; CP: Metabolism; knockout mouse; Lipid; lipidome; microbiome; phospholipase; polyunsaturated fatty acid; short-chain fatty acid; phospholipase; short-chain fatty acid; CP: Metabolism; colon; lipidome; microbiome; Lipid; polyunsaturated fatty acid; knockout mouse
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114752

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.
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•sPLA2-X deficiency worsens diet-induced obesity and colonic inflammation in C57BL/6 mice•sPLA2-X releases PUFAs and lysophospholipids in the colon•Lack of sPLA2-X decreases specific gut microbiota that produce SCFAs•sPLA2-X deficiency phenotypes are rescued by intake of ω3 PUFAs or SCFAs
Sato et al. show that obesity-related phenotypes in sPLA2-X-deficient C57BL/6 mice result from gut microbiota alteration. Colonic sPLA2-X releases ω3 PUFAs, ameliorates colonic inflammation, increases specific Clostridium species that produce SCFAs, and protects against diet-induced obesity and insulin resistance. Supplementation with ω3 PUFAs or SCFAs rescues the phenotypes caused by sPLA2-X deficiency.