High-Fat Diet Promotes DSS-Induced Ulcerative Colitis by Downregulated FXR Expression through the TGFB Pathway

Ulcerative colitis is one of the IBD which cause a chronic intestinal inflammation and dysfunctional of the mucosal barrier. For now, the incident of UC was steadily increased all over the world. It has become a novel independent risk factor of several severe diseases especially colon-rectal cancer....

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Bibliographic Details
Published in:	BioMed research international 2020, Vol.2020, p.3516128-7
Main Authors:	Zhao, Di, Cai, Chenwen, Chen, Qiyi, Jin, Shuang, Yang, Bo, Li, Ning
Format:	Article
Language:	eng
Subjects:	Acids Animals Antibodies Bile Caco-2 Cells Cellular signal transduction Colitis, Ulcerative - chemically induced Colitis, Ulcerative - genetics Colitis, Ulcerative - pathology Colon Colon cancer Development and progression Dextran Sulfate Diet Diet, High-Fat Disease Models, Animal Disease Progression Down-Regulation - genetics Etiology Genetic aspects Health aspects High fat diet Homeostasis Humans Immune system Inflammation Inflammatory bowel disease Inflammatory bowel diseases Intestine Laboratory animals Male Mice, Inbred C57BL Mucosa Pathogenesis Permeability Phenotypes Receptors, Cytoplasmic and Nuclear - agonists Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism Rectum Risk analysis Risk factors Signal Transduction Signs and symptoms Transforming Growth Factor beta - metabolism Transforming growth factor-b Transforming growth factors Ulcerative colitis Up-Regulation - genetics
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Summary:	Ulcerative colitis is one of the IBD which cause a chronic intestinal inflammation and dysfunctional of the mucosal barrier. For now, the incident of UC was steadily increased all over the world. It has become a novel independent risk factor of several severe diseases especially colon-rectal cancer. However, the etiology of UC was still obscure. Previous studies show that high-fat diet contributed to the pathogenesis of immune system dysregulation, and farnesoid X receptor (FXR) was also implicated in the pathogenesis of various inflammatory symptoms. Yet, their inner roles in the pathogenesis of UC have not been mentioned. In this study, we aim to investigate the role of FXR in UC. High-fat diet (HFD) promotes the progression of DSS-induced UC, shows an increasing secretion of bile acid in serum, and leads to a downregulation of FXR target genes (FXRα, Shp, and lbabp). Adding FXR agonist FexD rescues the phenotype induced by high-fat diet, whereas TGFBRI inhibitor SB431542 abrogates the restoration by FexD in DSS-induced UC mice. To further verify the relationship between the FXR and TGFB signaling pathway, we made a UC-HFD model in the Caco2 cell line. Results shows the same conclusion that FXR mitigate UC inflammation through a TGFB-dependent pathway. These results expand the role of FXR in ulcerative colitis and suggest that FXR activation may be considered a therapeutic strategy for UC.
ISSN:	2314-6133 2314-6141