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.
Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, School of Pharmacy, Showa University, Tokyo 142-8555, Japan.
Cell Rep. 2024 Oct 22;43(10):114752. doi: 10.1016/j.celrep.2024.114752. Epub 2024 Sep 17.
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 group X (sPLA-X) is abundantly expressed in colonic epithelial cells but is barely detectable in metabolic and immune tissues. Despite this distribution, sPLA-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-X orchestrates ω3 PUFA-SCFA interplay via modulation of the gut microbiota, thereby secondarily affecting systemic metabolism.
肠道微生物群影响宿主的生理功能，从维持局部肠道内稳态到全身免疫和代谢。分泌型磷脂酶 A 组 X（sPLA-X）在结肠上皮细胞中大量表达，但在代谢和免疫组织中几乎检测不到。尽管有这种分布，sPLA-X 缺陷（Pla2g10）小鼠表现出可变的肥胖相关表型，这些表型在抗生素治疗或与 Pla2g10 小鼠共笼后被消除，表明肠道微生物群的参与。在 Pla2g10 小鼠表现出饮食诱导肥胖和胰岛素抵抗加重的饲养条件下，它们表现出结肠炎症和上皮损伤增加、多不饱和脂肪酸（PUFA）和溶血磷脂产生减少、几种梭菌属物种丰度减少以及短链脂肪酸（SCFA）水平降低。通过用 ω3 PUFAs 或 SCFAs 进行饮食补充，可逆转 Pla2g10 小鼠的这些肥胖相关表型。因此，结肠 sPLA-X 通过调节肠道微生物群来协调 ω3 PUFAs-SCFA 相互作用，从而间接影响全身代谢。
