Amelioration of diabesity-induced colorectal ontogenesis by omega-3 fatty acids in mice
| Autor: | Betty Schwartz, Dana Davidovsky, Anna Algamas-Dimantov, Rachel Hertz, Julius Ben-Ari, Jacob Bar-Tana, Irena Peri, Jing X. Kang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
obesity
medicine.medical_specialty Colon Transgene Cellular differentiation Context (language use) QD415-436 Biology digestive system Biochemistry Mice Endocrinology Species Specificity epithelial cell growth Internal medicine Fatty Acids Omega-3 medicine Animals Intestinal Mucosa Research Articles Cell Proliferation Epithelial cell differentiation chemistry.chemical_classification diabetes Cell Differentiation Cell Biology Intestines Hepatocyte nuclear factors Phenotype Diabetes Mellitus Type 2 chemistry Immunology epithelial cell differentiation Signal transduction Stem cell colorectal neoplasia Signal Transduction Polyunsaturated fatty acid |
| Zdroj: | Journal of Lipid Research, Vol 53, Iss 6, Pp 1056-1070 (2012) |
| ISSN: | 0022-2275 |
| Popis: | Postnatal intestinal ontogenesis in an animal model of diabesity may recapitulate morphological and transduction features of diabesity-induced intestinal dysplasia and its amelioration by endogenous (n-3) polyunsaturated fatty acids (PUFA). Proliferation, differentiation, and transduction aspects of intestinal ontogenesis have been studied here in obese, insulin-resistant db/db mice, in fat-1 transgene coding for desaturation of (n-6) PUFA into (n-3) PUFA, in db/db crossed with fat-1 mice, and in control mice. Diabesity resulted in increased colonic proliferation and dedifferentiation of epithelial colonocytes and goblet cells, with increased colonic β-catenin and hepatocyte nuclear factor (HNF)-4α transcriptional activities accompanied by enrichment in HNF-4α–bound (n-6) PUFA. In contrast, in fat-1 mice, colonic proliferation was restrained, accompanied by differentiation of crypt stem cells into epithelial colonocytes and goblet cells and by decrease in colonic β-catenin and HNF-4α transcriptional activities, with concomitant enrichment in HNF-4α-bound (n-3) PUFA at the expense of (n-6) PUFA. Colonic proliferation and differentiation, the profile of β-catenin and HNF-4α-responsive genes, and the composition of HNF-4α-bound PUFA of db/db mice reverted to wild-type by introducing the fat-1 gene into the db/db context. Suppression of intestinal HNF-4α activity by (n-3) PUFA may ameliorate diabesity-induced intestinal ontogenesis and offer an effective preventive modality for colorectal cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|