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Overnutrition Stimulates Intestinal Epithelium Proliferation Through β-catenin Signaling in Obese Mice

Overnutrition Stimulates Intestinal Epithelium Proliferation Through β-catenin Signaling in Obese Mice

Jiaming Mao, Xiaomin Hu, Yao Xiao, Chao Yang, Yi Ding, Ning Hou, Jue Wang, Heping Cheng, Xiuqin Zhang

Diabetes. 2013 Nov;62(11):3736-46.

PMID: 23884889

Abstract:

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 β-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 β-catenin signaling. The β-catenin protein was upregulated along with inactivation of glycogen synthase kinase (GSK)-3β 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 β-catenin inhibitor JW55 (a small molecule that increases β-catenin degradation) in HFD mice. Parallel, in vitro experiments showed that β-catenin accumulation and cell proliferation stimulated by glucose were blocked by the β-catenin inhibitor FH535. And the GSK-3 inhibitor CHIR98014 in an intestinal epithelial cell line increased β-catenin accumulation and cyclin D1 expression. These results suggested that, besides contribution to intestinal development and homeostasis, GSK-3β/β-catenin signaling plays a central role in intestinal morphological and functional changes in response to overnutrition. Manipulating the GSK-3β/β-catenin signaling pathway in intestinal epithelium might become a therapeutic intervention for obesity induced by overnutrition.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP664993537	JW55		664993-53-7	Price

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