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Regulation of Gene Expression of Wnt signaling Pathway by Dietary High Fat and Effects on Colon Epithelia of Male Mice
Author(s) -
Xu Guanying,
Emmons Russel,
HernándezSaavedra Diego,
Kriska Adam,
Pan YuanXiang,
Chen Hong
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.643.22
Subject(s) - wnt signaling pathway , signal transduction , biology , endocrinology , medicine , lrp5 , microbiology and biotechnology , inflammation , lrp6 , gene expression , adipose tissue , wnt5a , gene , immunology , genetics
Diet induced obesity (DIO), resulting from long‐term consumption of a high fat diet, modifies multiple signaling pathways. Wnt signaling pathway is one of these response pathways that is closely associated with normal growth and maintenance of gut epithelia as well as gut inflammatory responses. There are two major types of Wnt signaling pathways, the canonical pathway and non‐canonical calcium dependent pathway. The two Wnt pathways interact with each other and play significant roles in cell development, stem cell maintenance, morphogenesis, cell differentiation, and inflammation. The main goal of this present study is to investigate the impact from diet‐induced obesity (DIO) on the regulation of gene expression involved in Wnt signaling and its role in the cellular development and inflammation of colon. In this study, 5‐week‐old male mice were fed either a control diet (CON, 10% kcal from fat) or a high‐fat diet (HF, 45% kcal from fat) for 11 weeks. Body composition and food intake were monitored regularly and colon tissue were collected directly after. MRI analysis of body composition showed that HF‐fed mice had a significantly higher % body fat (37.85% ± 0.56%) when compared to CON (28.13%±1.84%). Moreover, the effects of DIO in the cellular mRNA expression of Wnt‐pathway related genes were analyzed in the colon tissue from both control and high fat groups. The expression of Wnt signaling related genes including Gsk3 and c‐Myc was significantly decreased (p<0.05) in HF group. Wnt5a gene expression, which is associated to the non‐canonical pathway, was significantly decreased (p<0.05) in colon tissue of mice in the HF group, suggesting that both types of Wnt signaling pathway were suppressed by DIO. The repressed Wnt signaling could have significant impact on colon epithelial maintenance as well as inflammatory responses and is further investigated. Overall, DIO suppressed colonic gene expression of key factors of Wnt signaling pathways and this could cause dysregulation of inflammatory responses as well as colon epithelial injury.mWnt5a Normalized Quantity Mean Between CON and HF Group (n=6)mc‐Myc Normalized Quantity Mean Between CON and HF Group (n=6)mGSK3 Normalized Quantity Mean Between CON and HF Group (n=6)