Back to Search
Start Over
Genetic ablation of tumor necrosis factor-alpha attenuates the promoted colonic Wnt signaling in high fat diet-induced obese mice.
- Source :
-
Journal of Nutritional Biochemistry . Mar2020, Vol. 77, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
Abstract
- Obesity is an established risk factor for colorectal cancer, but the mechanisms responsible for this relationship are not adequately delineated. Using a TNF-α-/- mouse model, the present study aimed to test the causal role of TNF-α in mediating the promotion of tumorigenic Wnt signaling by high-fat diet-induced obesity. A 2×2 factorial study was performed with wild-type and TNF-α-/- mice on a 60 kcal% high-fat diet or a 10 kcal% low-fat diet. The inflammatory cytokine profile and genes within the Wnt signaling pathway were measured by electrochemiluminescence assay, real-time PCR, Western blotting or immunohistochemistry. The high-fat diet increased body weights in both wild-type and TNF-α-/- animals (P<.05), but males were more sensitive to high-fat diet-induced weight gain and increases of colonic TNF-α than females (P<.05). Genetic ablation of TNF-α suppressed the obesity-promoted elevation of Wnt signaling, as indicated by decreased levels of phospho-GSK3β and active β-catenin, two key components within the Wnt pathway (P<.05). The transcriptional expression of several Wnt signaling targets (C-myc, Cyclin D1 and Axin 2) and cell proliferation, as indicated by Ki-67 staining, were attenuated by the deletion of TNF-α in the high-fat-fed TNF-α-/- animals comparing with the wild-type animals (P<.05). Our data collectively showed that the genetic deletion of TNF-α attenuated the tumorigenic Wnt signaling, which was otherwise elevated by high-fat diet-induced obesity, and demonstrated a causal role of TNF-α in mediating obesity-associated Wnt signaling, which indicates a potential mechanism of inflammation-driven Wnt signaling for obesity-associated colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]
- Subjects :
- *WNT signal transduction
*LOW-fat diet
*HIGH-fat diet
*WNT genes
*WEIGHT gain
*ELECTROLUMINESCENT polymers
*OBESITY complications
*OBESITY
*CYTOKINES
*RESEARCH
*COLON (Anatomy)
*BODY weight
*INFLAMMATION
*ANIMAL experimentation
*RESEARCH methodology
*ANIMAL nutrition
*CELL physiology
*APOPTOSIS
*EVALUATION research
*MEDICAL cooperation
*CELLULAR signal transduction
*COLORECTAL cancer
*COMPARATIVE studies
*TUMOR necrosis factors
*LIGHT
*GENOTYPES
*GENETIC techniques
*MICE
*DISEASE complications
Subjects
Details
- Language :
- English
- ISSN :
- 09552863
- Volume :
- 77
- Database :
- Academic Search Index
- Journal :
- Journal of Nutritional Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 141809929
- Full Text :
- https://doi.org/10.1016/j.jnutbio.2019.108302