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Suppression of GHS-R in AgRP neurons mitigates diet-induced obesity by activating thermogenesis
Wu C.-S.5; Bongmba O.Y.N.1; Yue J.1; Lee J.H.1; Lin L.1; Saito K.1; Pradhan G.1; Li D.-P.4; Pan H.-L.4; Xu A.3; Guo S.5; Xu Y.1; Sun Y.5
2017-04-14
Source PublicationInternational Journal of Molecular Sciences
ISSN14220067 16616596
Volume18Issue:4
Abstract

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). 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) Diet-induced Obesity (Dio) Ghrelin Growth Hormone Secretagogue Receptor (Ghs-r) 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
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWu C.-S.; Bongmba O.Y.N.; Yue J.; Lee J.H.; Lin L.; Saito K.; Pradhan G.; Li D.-P.; Pan H.-L.; Xu A.; Guo S.; Xu Y.; Sun Y.
Affiliation1.Baylor College of Medicine
2.Huazhong University of Science and Technology
3.University of California, San Francisco
4.University of Texas MD Anderson Cancer Center
5.Texas A and M University
6.Gachon University
7.Universidade de Macau
Recommended Citation
GB/T 7714
Wu C.-S.,Bongmba O.Y.N.,Yue J.,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 C.-S..,Bongmba O.Y.N..,Yue J..,Lee J.H..,Lin L..,...&Sun Y..(2017).Suppression of GHS-R in AgRP neurons mitigates diet-induced obesity by activating thermogenesis.International Journal of Molecular Sciences,18(4).
MLA Wu C.-S.,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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