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KMID : 1140220210260010032
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대한암예방학회지
2021 Volume.26 No. 1 p.32 ~ p.40
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Dysregulated Free Fatty Acid Receptor 2 Exacerbates Colonic Adenoma Formation in ApcMin/+ Mice: Relation to Metabolism and Gut Microbiota Composition
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Huang Yi-Wen
Lin Chien-Wei
Pan Pan
Echeveste Carla Elena
Dong Athena
Oshima Kiyoko
Yearsley Martha
Yu Jianhua
Wang Li-Shu
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Abstract
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Free fatty acid receptor 2 (FFAR2) has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of FFAR2 signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model (ApcMin/+). Ffar2 deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, ApcMin/+, and ApcMin/+-Ffar2-/- mice. The relative abundance of Flavobacteriaceae and Verrucomicrobiaceae was significantly increased in the ApcMin/+-Ffar2-/- mice compared to the ApcMin/+ mice. In addition, knocking-down FFAR2 in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, longchain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that Ffar2 deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.
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KEYWORD
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Ffar2, ApcMin/+, Colorectal cancer, Metabolomics, Gut microbiota
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