详细记录  
题名:Overnutrition Stimulates Intestinal Epithelium Proliferation Through beta-Catenin Signaling in Obese Mice.
作者:MAO J; HU X; XIAO Y; YANG C; DING Y; HOU N; WANG J; CHENG H; ZHANG X;
来源:Diabetes. 2013 Nov;62(11):3736-46. doi: 10.2337/db13-0035. Epub 2013 Jul 24. [ IF= 7.89 ] ]
URL :10.2337/db13-0035
日期:20131203
摘要: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.

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