期刊
DIABETES
卷 68, 期 6, 页码 1197-1209出版社
AMER DIABETES ASSOC
DOI: 10.2337/db18-1321
关键词
-
资金
- National Key R&D Program of China [2017YFC0908900]
- National Natural Science Foundation of China [81500619, 81730020, 81870405]
- Natural Science Foundation of Guangdong Province [2016A030310040]
- Shenzhen Science and Technology Project [JCYJ20160422091658982, JCYJ20160422153856130]
ZnT8 is a zinc transporter enriched in pancreatic beta-cells, and its polymorphism is associated with increased susceptibility to type 2 diabetes. However, the exact role of ZnT8 in systemic energy metabolism remains elusive. In this study, we found that ZnT8 knockout mice displayed increased adiposity without obvious weight gain. We also observed that the intestinal tract morphology, motility, and gut microbiota were changed in ZnT8 knockout mice. Further study demonstrated that ZnT8 was expressed in enteroendocrine cells, especially in 5-hydroxytryptamine (5-HT)-positive enterochromaffin cells. Lack of ZnT8 resulted in an elevated circulating 5-HT level owing to enhanced expression of tryptophan hydroxylase 1. Blocking 5-HT synthesis in ZnT8-deficient mice restored adiposity, high-fat diet-induced obesity, and glucose intolerance. Moreover, overexpression of human ZnT8 diabetes high-risk allele R325W increased 5-HT levels relative to the low-risk allele in RIN14B cells. Our study revealed an unexpected role of ZnT8 in regulating peripheral 5-HT biogenesis and intestinal microenvironment, which might contribute to the increased risk of obesity and type 2 diabetes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据