Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon

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Dermadi , D , Valo , S , Ollila , S , Soliymani , R , Sipari , N , Pussila , M , Sarantaus , L , Linden , J , Baumann , M & Nystrom , M 2017 , ' Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon ' , Cancer Research , vol. 77 , no. 12 , pp. 3352-3363 . https://doi.org/10.1158/0008-5472.CAN-16-2860

Title: Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon
Author: Dermadi, Denis; Valo, Satu; Ollila, Saara; Soliymani, Rabah; Sipari, Nina; Pussila, Marjaana; Sarantaus, Laura; Linden, Jere; Baumann, Marc; Nystrom, Minna
Contributor: University of Helsinki, Biosciences
University of Helsinki, Medicum
University of Helsinki, Research Programs Unit
University of Helsinki, Medicum
University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, Medicum
University of Helsinki, Biosciences
Date: 2017-06-15
Language: eng
Number of pages: 12
Belongs to series: Cancer Research
ISSN: 0008-5472
URI: http://hdl.handle.net/10138/237004
Abstract: Western-style diets (WD) high in fat and scarce in fiber and vitamin D increase risks of colorectal cancer. Here, we performed a long-term diet study in mice to follow tumorigenesis and characterize structural and metabolic changes in colon mucosa associated with WD and predisposition to colorectal cancer. WD increased colon tumor numbers, and mucosa proteomic analysis indicated severe deregulation of intracellular bile acid (BA) homeostasis and activation of cell proliferation. WD also in-creased crypt depth and colon cell proliferation. Despite increased luminal BA, colonocytes from WD-fed mice exhibited decreased expression of the BA transporters FABP6, OST beta, and ASBT and decreased concentrations of secondary BA deoxycholic acid and lithocholic acid, indicating reduced activity of the nuclear BA receptor FXR. Overall, our results suggest that WD increases cancer risk by FXR inactivation, leading to BA deregulation and increased colon cell proliferation. (C) 2017 AACR.
Subject: FARNESOID-X RECEPTOR
NEGATIVE FEEDBACK-REGULATION
NUCLEAR RECEPTOR
BINDING PROTEIN
DOWN-REGULATION
HIGH-FAT
TRANSPORTER
CANCER
MICE
INTESTINE
3122 Cancers
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