AUTHOR=Chen Xi , Yin Lin , Jia Wei-hua , Wang Nuo-qi , Xu Chun-yang , Hou Bi-yu , Li Na , Zhang Li , Qiang Gui-fen , Yang Xiu-ying , Du Guan-hua 

TITLE=Chronic Urotensin-II Administration Improves Whole-Body Glucose Tolerance in High-Fat Diet-Fed Mice

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00453

DOI=10.3389/fendo.2019.00453

ISSN=1664-2392

ABSTRACT=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 usage as well as mitochondrial respiratory function. In this study, we found that chronic U-II administration (more than seven days) ameliorated glucose tolerance in high-fat diet-fed mice. In addition, chronic U-II administration reduced weight gain and adipose tissue weights, including that of visceral, subcutaneous and brown fat, but without a significant change in blood lipid levels. These were accompanied by 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 with increased aerobic respiration in C2C12 cells. Taken together, chronic U-II stimulation leads to improvement on glucose tolerance in high-fat diet-fed mice and this effect maybe closely related with the reduction in adipose tissue weights and enhancement on energy substrates usage in skeletal muscle.