author_facet Zhang, Lei
Riepler, Sabrina J.
Turner, Nigel
Enriquez, Ronaldo F.
Lee, I-Chieh J.
Baldock, Paul A.
Herzog, Herbert
Sainsbury, Amanda
Zhang, Lei
Riepler, Sabrina J.
Turner, Nigel
Enriquez, Ronaldo F.
Lee, I-Chieh J.
Baldock, Paul A.
Herzog, Herbert
Sainsbury, Amanda
author Zhang, Lei
Riepler, Sabrina J.
Turner, Nigel
Enriquez, Ronaldo F.
Lee, I-Chieh J.
Baldock, Paul A.
Herzog, Herbert
Sainsbury, Amanda
spellingShingle Zhang, Lei
Riepler, Sabrina J.
Turner, Nigel
Enriquez, Ronaldo F.
Lee, I-Chieh J.
Baldock, Paul A.
Herzog, Herbert
Sainsbury, Amanda
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
Physiology (medical)
Physiology
author_sort zhang, lei
spelling Zhang, Lei Riepler, Sabrina J. Turner, Nigel Enriquez, Ronaldo F. Lee, I-Chieh J. Baldock, Paul A. Herzog, Herbert Sainsbury, Amanda 0363-6119 1522-1490 American Physiological Society Physiology (medical) Physiology http://dx.doi.org/10.1152/ajpregu.00345.2010 <jats:p> 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<jats:sup>−/−</jats:sup> and particularly in Y2<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> but not in Y2<jats:sup>−/−</jats:sup> mice, suggesting a critical role of Y4 signaling and synergistic interactions with Y2 signaling in the regulation of energy expenditure and physical activity. Y2<jats:sup>−/−</jats:sup> and Y4<jats:sup>−/−</jats:sup> mice also exhibited a decrease in respiratory exchange ratio with no further synergistic decrease in Y2<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> 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<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> but not Y2<jats:sup>−/−</jats:sup> or Y4<jats:sup>−/−</jats:sup> mice showed significant increases in muscle protein levels of peroxisome proliferator-activated receptor (PPAR)γ coactivator (PGC)-1α, 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. </jats:p> Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
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title Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_unstemmed Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_full Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_fullStr Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_full_unstemmed Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_short Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_sort y2 and y4 receptor signaling synergistically act on energy expenditure and physical activity
topic Physiology (medical)
Physiology
url http://dx.doi.org/10.1152/ajpregu.00345.2010
publishDate 2010
physical R1618-R1628
description <jats:p> 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<jats:sup>−/−</jats:sup> and particularly in Y2<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> but not in Y2<jats:sup>−/−</jats:sup> mice, suggesting a critical role of Y4 signaling and synergistic interactions with Y2 signaling in the regulation of energy expenditure and physical activity. Y2<jats:sup>−/−</jats:sup> and Y4<jats:sup>−/−</jats:sup> mice also exhibited a decrease in respiratory exchange ratio with no further synergistic decrease in Y2<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> 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<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> but not Y2<jats:sup>−/−</jats:sup> or Y4<jats:sup>−/−</jats:sup> mice showed significant increases in muscle protein levels of peroxisome proliferator-activated receptor (PPAR)γ coactivator (PGC)-1α, 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. </jats:p>
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author Zhang, Lei, Riepler, Sabrina J., Turner, Nigel, Enriquez, Ronaldo F., Lee, I-Chieh J., Baldock, Paul A., Herzog, Herbert, Sainsbury, Amanda
author_facet Zhang, Lei, Riepler, Sabrina J., Turner, Nigel, Enriquez, Ronaldo F., Lee, I-Chieh J., Baldock, Paul A., Herzog, Herbert, Sainsbury, Amanda, Zhang, Lei, Riepler, Sabrina J., Turner, Nigel, Enriquez, Ronaldo F., Lee, I-Chieh J., Baldock, Paul A., Herzog, Herbert, Sainsbury, Amanda
author_sort zhang, lei
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container_title American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
container_volume 299
description <jats:p> 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<jats:sup>−/−</jats:sup> and particularly in Y2<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> but not in Y2<jats:sup>−/−</jats:sup> mice, suggesting a critical role of Y4 signaling and synergistic interactions with Y2 signaling in the regulation of energy expenditure and physical activity. Y2<jats:sup>−/−</jats:sup> and Y4<jats:sup>−/−</jats:sup> mice also exhibited a decrease in respiratory exchange ratio with no further synergistic decrease in Y2<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> 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<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> but not Y2<jats:sup>−/−</jats:sup> or Y4<jats:sup>−/−</jats:sup> mice showed significant increases in muscle protein levels of peroxisome proliferator-activated receptor (PPAR)γ coactivator (PGC)-1α, 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. </jats:p>
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spelling Zhang, Lei Riepler, Sabrina J. Turner, Nigel Enriquez, Ronaldo F. Lee, I-Chieh J. Baldock, Paul A. Herzog, Herbert Sainsbury, Amanda 0363-6119 1522-1490 American Physiological Society Physiology (medical) Physiology http://dx.doi.org/10.1152/ajpregu.00345.2010 <jats:p> 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<jats:sup>−/−</jats:sup> and particularly in Y2<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> but not in Y2<jats:sup>−/−</jats:sup> mice, suggesting a critical role of Y4 signaling and synergistic interactions with Y2 signaling in the regulation of energy expenditure and physical activity. Y2<jats:sup>−/−</jats:sup> and Y4<jats:sup>−/−</jats:sup> mice also exhibited a decrease in respiratory exchange ratio with no further synergistic decrease in Y2<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> 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<jats:sup>−/−</jats:sup>Y4<jats:sup>−/−</jats:sup> but not Y2<jats:sup>−/−</jats:sup> or Y4<jats:sup>−/−</jats:sup> mice showed significant increases in muscle protein levels of peroxisome proliferator-activated receptor (PPAR)γ coactivator (PGC)-1α, 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. </jats:p> Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
spellingShingle Zhang, Lei, Riepler, Sabrina J., Turner, Nigel, Enriquez, Ronaldo F., Lee, I-Chieh J., Baldock, Paul A., Herzog, Herbert, Sainsbury, Amanda, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity, Physiology (medical), Physiology
title Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_full Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_fullStr Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_full_unstemmed Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_short Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
title_sort y2 and y4 receptor signaling synergistically act on energy expenditure and physical activity
title_unstemmed Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity
topic Physiology (medical), Physiology
url http://dx.doi.org/10.1152/ajpregu.00345.2010