Chronic Urotensin-II Administration Improves Whole-Body Glucose Tolerance in High-Fat Diet-Fed Mice
Chronic Urotensin-II Administration Improves Whole-Body Glucose Tolerance in High-Fat Diet-Fed Mice
复制标题
长期给予尾加压素-II 可改善高脂饮食喂养小鼠的全身葡萄糖耐量
DOI：
10.3389/fendo.2019.00453
复制
发表时间：
2019-07-12
影响因子：
5.2
通讯作者：
Du, Guan-hua
中科院分区：
文献类型：
--
作者：
Chen, Xi;Yin, Lin;Du, Guan-hua
尿紧张素- ii （U-II）是G蛋白偶联受体-尿紧张素受体的内源性肽激动剂。关于U-II对血糖的影响，有许多相互矛盾的发现。本研究旨在探讨U-II对高脂饮食小鼠葡萄糖代谢的影响。雄性C57BL/6J小鼠分别饲喂45%高脂日粮和低脂日粮，腹腔注射U-II进行体内研究。用骨骼肌C2C12细胞测定U-II对葡萄糖和脂肪酸代谢以及线粒体呼吸功能的影响。在这项研究中，我们发现慢性U-II给药（超过7天）改善了高脂肪饮食小鼠的葡萄糖耐量。此外，慢性U-II给药减少了体重增加和脂肪组织重量，包括内脏、皮下和棕色脂肪组织，而血脂水平没有明显变化。同时骨骼肌线粒体产热基因Ucp3 mRNA表达增加。此外，体外U-II处理直接增加了C2C12细胞的葡萄糖和游离脂肪酸消耗，增加了有氧呼吸。综上所述，慢性U-II刺激导致高脂饮食小鼠葡萄糖耐量的改善，这种效果可能与脂肪组织重量的减少和骨骼肌能量底物利用的增强密切相关。
Urotensin-II (U-II) is an endogenous peptide agonist of a G protein-coupled receptor-urotensin receptor. There are many conflicting findings about the effects of U-II on blood glucose. This study aims to explore the effects of U-II on glucose metabolism in high-fat diet-fed mice. Male C57BL/6J mice were fed a 45% high-fat diet or chow diet and were administered U-II intraperitoneally for in vivo study. Skeletal muscle C2C12 cells were used to determine the effects of U-II on glucose and fatty acid metabolismas well as mitochondrial respiratory function. In this study, we found that chronic U-II administration (more than 7 days) ameliorated glucose tolerance in high-fat diet-fed mice. In addition, chronic U-II administration reduced the weight gain and the adipose tissue weight, including visceral, subcutaneous, and brown adipose tissue, without a significant change in blood lipid levels. These were accompanied by the increased mRNA expression of the mitochondrial thermogenesis gene Ucp3 in skeletal muscle. Furthermore, in vitro treatment with U-II directly enhanced glucose and free fatty acid consumption in C2C12 cells with increased aerobic respiration. Taken together, chronic U-II stimulation leads to improvement on glucose tolerance in high-fat diet-fed mice and this effect maybe closely related to the reduction in adipose tissue weights and enhancement on energy substrate utilization in skeletal muscle.