Next Article in Journal
Potential Role of Free Fatty Acids in the Pathogenesis of Periodontitis and Primary Sjögren’s Syndrome
Next Article in Special Issue
Clarifying the Ghrelin System’s Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand
Previous Article in Journal
Skeletal Muscle Nucleo-Mitochondrial Crosstalk in Obesity and Type 2 Diabetes
Previous Article in Special Issue
Therapeutic Potential of Targeting the Ghrelin Pathway
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(4), 832;

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

Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA
United States Department of Agriculture/Agriculture Research Service Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
Reproductive Medical Center, Tongji affiliated Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
College of Pharmacy, Gachon University, Incheon 21936, Korea
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA
Division of Anesthesiology and Critical Care, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Diabetes Center, University of California, San Francisco, CA 94143, USA
Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Suzanne L. Dickson
Received: 1 March 2017 / Revised: 7 April 2017 / Accepted: 7 April 2017 / Published: 14 April 2017
(This article belongs to the Special Issue Neurobiological Perspectives on Ghrelin)
Full-Text   |   PDF [2111 KB, uploaded 14 April 2017]   |  


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;Ghsrf/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. View Full-Text
Keywords: Agouti-related peptide (AgRP); ghrelin; growth hormone secretagogue receptor (GHS-R); diet-induced obesity (DIO); thermogenesis Agouti-related peptide (AgRP); ghrelin; growth hormone secretagogue receptor (GHS-R); diet-induced obesity (DIO); thermogenesis

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Wu, 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. Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating Thermogenesis. Int. J. Mol. Sci. 2017, 18, 832.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top