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

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http://hdl.handle.net/10138/237004

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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

Titel: Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and Tumorigenesis in Colon
Författare: Dermadi, Denis; Valo, Satu; Ollila, Saara; Soliymani, Rabah; Sipari, Nina; Pussila, Marjaana; Sarantaus, Laura; Linden, Jere; Baumann, Marc; Nystrom, Minna
Upphovmannens organisation: Biosciences
Medicum
Department of Medical and Clinical Genetics
Research Programs Unit
Department of Biochemistry and Developmental Biology
Genetics
Departments of Faculty of Veterinary Medicine
Veterinary Pathology and Parasitology
Veterinary Biosciences
Marc Baumann / Principal Investigator
Minna Nyström / Principal Investigator
Datum: 2017-06-15
Språk: eng
Sidantal: 12
Tillhör serie: Cancer Research
ISSN: 0008-5472
DOI: https://doi.org/10.1158/0008-5472.CAN-16-2860
Permanenta länken (URI): http://hdl.handle.net/10138/237004
Abstrakt: 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
Referentgranskad: Ja
Licens: unspecified
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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