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Dysregulated Free Fatty Acid Receptor 2 Exacerbates Colonic Adenoma Formation in ApcMin/+ Mice: Relation to Metabolism and Gut Microbiota Composition

Journal of Cancer Prevention 2021년 26권 1호 p.32 ~ 40
Huang Yi-Wen, Lin Chien-Wei, Pan Pan, Echeveste Carla Elena, Dong Athena, Oshima Kiyoko, Yearsley Martha, Yu Jianhua, Wang Li-Shu,
소속 상세정보
 ( Huang Yi-Wen ) - Medical College of Wisconsin Department of Obstetrics and Gynecology
 ( Lin Chien-Wei ) - Medical College of Wisconsin Division of Biostatistics
 ( Pan Pan ) - Medical College of Wisconsin Department of Medicine
 ( Echeveste Carla Elena ) - Medical College of Wisconsin Department of Medicine
 ( Dong Athena ) - Medical College of Wisconsin Department of Medicine
 ( Oshima Kiyoko ) - Johns Hopkins University School of Medicine Department of Pathology
 ( Yearsley Martha ) - Ohio State University Department of Pathology
 ( Yu Jianhua ) - City of Hope National Medical Center Department of Hematology and Hematopoietic Cell Transplantation
 ( Wang Li-Shu ) - Medical College of Wisconsin Department of Medicine

Abstract


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.

키워드

Ffar2, ApcMin/+; Colorectal cancer; Metabolomics; Gut microbiota

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