| First Author | Algamas-Dimantov A | Year | 2012 |
| Journal | J Lipid Res | Volume | 53 |
| Issue | 6 | Pages | 1056-70 |
| PubMed ID | 22357704 | Mgi Jnum | J:184929 |
| Mgi Id | MGI:5426748 | Doi | 10.1194/jlr.M021949 |
| Citation | Algamas-Dimantov A, et al. (2012) Amelioration of diabesity-induced colorectal ontogenesis by omega-3 fatty acids in mice. J Lipid Res 53(6):1056-70 |
| abstractText | 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 beta-catenin and hepatocyte nuclear factor (HNF)-4alpha transcriptional activities accompanied by enrichment in HNF-4alpha-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 beta-catenin and HNF-4alpha transcriptional activities, with concomitant enrichment in HNF-4alpha-bound (n-3) PUFA at the expense of (n-6) PUFA. Colonic proliferation and differentiation, the profile of beta-catenin and HNF-4alpha-responsive genes, and the composition of HNF-4alpha-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-4alpha activity by (n-3) PUFA may ameliorate diabesity-induced intestinal ontogenesis and offer an effective preventive modality for colorectal cancer. |
