TY - JOUR AU - Chen, Xi AU - Yin, Lin AU - Jia, Wei-hua AU - Wang, Nuo-qi AU - Xu, Chun-yang AU - Hou, Bi-yu AU - Li, Na AU - Zhang, Li AU - Qiang, Gui-fen AU - Yang, Xiu-ying AU - Du, Guan-hua PY - 2019 M3 - Original Research TI - Chronic Urotensin-II Administration Improves Whole-Body Glucose Tolerance in High-Fat Diet-Fed Mice JO - Frontiers in Endocrinology UR - https://www.frontiersin.org/articles/10.3389/fendo.2019.00453 VL - 10 SN - 1664-2392 N2 - 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 metabolism as 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. ER -