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Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis

Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in...

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Autores principales: Wu, Chia-Shan, Bongmba, Odelia Y. N., Yue, Jing, Lee, Jong Han, Lin, Ligen, Saito, Kenji, Pradhan, Geetali, Li, De-Pei, Pan, Hui-Lin, Xu, Allison, Guo, Shaodong, Xu, Yong, Sun, Yuxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412416/
https://www.ncbi.nlm.nih.gov/pubmed/28420089
http://dx.doi.org/10.3390/ijms18040832
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author Wu, Chia-Shan
Bongmba, Odelia Y. N.
Yue, Jing
Lee, Jong Han
Lin, Ligen
Saito, Kenji
Pradhan, Geetali
Li, De-Pei
Pan, Hui-Lin
Xu, Allison
Guo, Shaodong
Xu, Yong
Sun, Yuxiang
author_facet Wu, Chia-Shan
Bongmba, Odelia Y. N.
Yue, Jing
Lee, Jong Han
Lin, Ligen
Saito, Kenji
Pradhan, Geetali
Li, De-Pei
Pan, Hui-Lin
Xu, Allison
Guo, Shaodong
Xu, Yong
Sun, Yuxiang
author_sort Wu, Chia-Shan
collection PubMed
description Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis. To further decipher the specific neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsr(f/f)). Our data showed that GHS-R in AgRP neurons is required for ghrelin’s stimulatory effects on growth hormone secretion, acute food intake and adiposity, but not for long-term total food intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced thermogenic activation in both brown and subcutaneous fat; this implies that GHS-R suppression in AgRP neurons enhances sympathetic outflow. In summary, our results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis, and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing energy utilization and pathogenesis of DIO.
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spelling pubmed-54124162017-05-05 Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis Wu, Chia-Shan Bongmba, Odelia Y. N. Yue, Jing Lee, Jong Han Lin, Ligen Saito, Kenji Pradhan, Geetali Li, De-Pei Pan, Hui-Lin Xu, Allison Guo, Shaodong Xu, Yong Sun, Yuxiang Int J Mol Sci Article Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis. To further decipher the specific neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsr(f/f)). Our data showed that GHS-R in AgRP neurons is required for ghrelin’s stimulatory effects on growth hormone secretion, acute food intake and adiposity, but not for long-term total food intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced thermogenic activation in both brown and subcutaneous fat; this implies that GHS-R suppression in AgRP neurons enhances sympathetic outflow. In summary, our results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis, and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing energy utilization and pathogenesis of DIO. MDPI 2017-04-14 /pmc/articles/PMC5412416/ /pubmed/28420089 http://dx.doi.org/10.3390/ijms18040832 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Chia-Shan
Bongmba, Odelia Y. N.
Yue, Jing
Lee, Jong Han
Lin, Ligen
Saito, Kenji
Pradhan, Geetali
Li, De-Pei
Pan, Hui-Lin
Xu, Allison
Guo, Shaodong
Xu, Yong
Sun, Yuxiang
Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis
title Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis
title_full Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis
title_fullStr Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis
title_full_unstemmed Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis
title_short Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis
title_sort suppression of ghs-r in agrp neurons mitigates diet-induced obesity by activating thermogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412416/
https://www.ncbi.nlm.nih.gov/pubmed/28420089
http://dx.doi.org/10.3390/ijms18040832
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