Dysregulated Free Fatty Acid Receptor 2 Exacerbates Colonic Adenoma Formation in ApcMin/+ Mice: Relation to Metabolism and Gut Microbiota Composition
10.15430/JCP.2021.26.1.32
- Author:
Yi-Wen HUANG
1
;
Chien-Wei LIN
;
Pan PAN
;
Carla Elena ECHEVESTE
;
Athena DONG
;
Kiyoko OSHIMA
;
Martha YEARSLEY
;
Jianhua YU
;
Li-Shu WANG
Author Information
1. Department of Obstetrics & Gynecology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
- Publication Type:Original Article
- From:Journal of Cancer Prevention
2021;26(1):32-40
- CountryRepublic of Korea
- Language:English
-
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.
