UM
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
2017-04
Source PublicationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN1422-0067
Volume18Issue:4
AbstractGhrelin, 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.
KeywordAgouti-related peptide (AgRP) ghrelin growth hormone secretagogue receptor (GHS-R) diet-induced obesity (DIO) thermogenesis
DOI10.3390/ijms18040832
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS IDWOS:000402639400156
PublisherMDPI AG
The Source to ArticleWOS
Fulltext Access
Citation statistics
Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Wu, Chia-Shan,Bongmba, Odelia Y. N.,Yue, Jing,et al. Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2017,18(4).
APA Wu, Chia-Shan.,Bongmba, Odelia Y. N..,Yue, Jing.,Lee, Jong Han.,Lin, Ligen.,...&Sun, Yuxiang.(2017).Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,18(4).
MLA Wu, Chia-Shan,et al."Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 18.4(2017).
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