| First Author | Mao J | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 11 | Pages | 3736-46 |
| PubMed ID | 23884889 | Mgi Jnum | J:208939 |
| Mgi Id | MGI:5565414 | Doi | 10.2337/db13-0035 |
| Citation | Mao J, et al. (2013) Overnutrition stimulates intestinal epithelium proliferation through beta-catenin signaling in obese mice. Diabetes 62(11):3736-46 |
| abstractText | Obesity is a major risk factor for type 2 diabetes and cardiovascular diseases. And overnutrition is a leading cause of obesity. After most nutrients are ingested, they are absorbed in the small intestine. Signals from beta-catenin are essential to maintain development of the small intestine and homeostasis. In this study, we used a hyperphagia db/db obese mouse model and a high-fat diet (HFD)-induced obesity mouse model to investigate the effects of overnutrition on intestinal function and beta-catenin signaling. The beta-catenin protein was upregulated along with inactivation of glycogen synthase kinase (GSK)-3beta in the intestines of both db/db and HFD mice. Proliferation of intestinal epithelial stem cells, villi length, nutrient absorption, and body weight also increased in both models. These changes were reversed by caloric restriction in db/db mice and by beta-catenin inhibitor JW55 (a small molecule that increases beta-catenin degradation) in HFD mice. Parallel, in vitro experiments showed that beta-catenin accumulation and cell proliferation stimulated by glucose were blocked by the beta-catenin inhibitor FH535. And the GSK-3 inhibitor CHIR98014 in an intestinal epithelial cell line increased beta-catenin accumulation and cyclin D1 expression. These results suggested that, besides contribution to intestinal development and homeostasis, GSK-3beta/beta-catenin signaling plays a central role in intestinal morphological and functional changes in response to overnutrition. Manipulating the GSK-3beta/beta-catenin signaling pathway in intestinal epithelium might become a therapeutic intervention for obesity induced by overnutrition. |
