4.3 Article

Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00345.2010

关键词

neuropeptide Y receptors; lipid oxidation; lean and fat tissue mass

资金

  1. National Health and Medical Research Council (NHMRC) of Australia

向作者/读者索取更多资源

Zhang L, Riepler SJ, Turner N, Enriquez RF, Lee ICJ, Baldock PA, Herzog H, Sainsbury A. Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity. Am J Physiol Regul Integr Comp Physiol 299: R1618-R1628, 2010. First published September 29, 2010; doi:10.1152/ajpregu.00345.2010.-Neuropeptide Y receptors are critical regulators of energy homeostasis and are well known for their powerful influence on feeding, but their roles in other important aspects of energy homeostasis, such as energy expenditure and their functional interactions in these processes, are largely unknown. Here we show that mice lacking both Y2 and Y4 receptors exhibited a reduction in adiposity, more prominent in intra-abdominal vs. subcutaneous fat, and an increase in lean mass as determined by dual-energy X-ray absorptiometry. These changes were more pronounced than those seen in mice with Y2 or Y4 receptor single deletion, demonstrating the important roles and synergy of Y2 and Y4 signaling in the regulation of body composition. These changes in body composition occurred without significant changes in food intake, but energy expenditure and physical activity were significantly increased in Y4(-/-) and particularly in Y2(-/-)Y4(-/-) but not in Y2(-/-) mice, suggesting a critical role of Y4 signaling and synergistic interactions with Y2 signaling in the regulation of energy expenditure and physical activity. Y2(-/-) and Y4(-/-) mice also exhibited a decrease in respiratory exchange ratio with no further synergistic decrease in Y2(-/-)Y4(-/-) mice, suggesting that Y2 and Y4 signaling each play important and independent roles in the regulation of substrate utilization. The synergy between Y2 and Y4 signaling in regulating fat mass may be related to differences in mitochondrial oxidative capacity, since Y2(-/-)Y4(-/-) but not Y2(-/-) or Y4(-/-) mice showed significant increases in muscle protein levels of peroxisome proliferator-activated receptor (PPAR)gamma coactivator (PGC)-1 alpha, and mitochondrial respiratory chain complexes I and III. Taken together, this work demonstrates the critical roles of Y2 and Y4 receptors in the regulation of body composition and energy metabolism, highlighting dual antagonism of Y2 and Y4 receptors as a potentially effective anti-obesity treatment.

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。

评论

主要评分

4.3
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据