| GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility. | |
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MedLine Citation:
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PMID: 22829581 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucagon-like peptides (GLP-1/2) are cosecreted from endocrine L cells in the gut and preproglucagonergic neurons in the brain. Peripheral GLP-2 action is essential for maintaining intestinal homeostasis, improving absorption efficiency and blood flow, promoting immune defense, and producing efficacy in treatment of gastrointestinal diseases. However, it is unknown if CNS GLP-2 plays a physiological role in the control of energy homeostasis. Since GLP-1/2 are cotranslated from preproglucagongene and coproduced by prohormone convertase-1, it is challenging to knockout GLP-2 only. Instead, our laboratory has generated a Glp2r-floxed mouse line to dissect cell-specific GLP-2 receptor GLP-2R) action in the regulation of energy balance. Our objective was to determine if GLP-2R in the hypothalamus modulates feeding behavior and gastric emptying. We show that Glp2r mRNA and protein are highly expressed in the arcuate nucleus and dorsomedial nucleus of the mouse hypothalamus. Using the Cre-LoxP system, we generated mice that lack Glp2r expression in POMC neurons (KO; mainly in the hypothalamus). The KO mice showed hyperphagic behavior (such as increases in food intake and meal frequency), accelerated gastric emptying (assessed by [(13)C]octanoic acid breath test), and late-onset obesity, yet there was no decrease in basal metabolic rate. Infusion of GLP-2 (2.5 nmol into the 4th ventricle) suppressed food intake and gastric emptying, while GLP-2-mediated effects were abolished in the melanocortin receptor-4 (MC4R) KO mice. We conclude that Glp2r deletion in POMC neurons enhances feeding behavior and gastric motility, whereas icv GLP-2R activation suppresses food intake and gastric emptying through the MC4R signaling pathway. This study indicates that CNS GLP-2R plays a physiological role in the control of feeding behavior and gastric emptying and that this is mediated probably through the melanocortin system. |
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Authors:
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Xinfu Guan; Xuemei Shi; Xiaojie Li; Benny Chang; Yi Wang; Depei Li; Lawrence Chan |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-07-24 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 303 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-02 Completed Date: 2013-01-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E853-64 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, US Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center, TX 77030, USA. xguan@bcm.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arcuate Nucleus / physiology Dorsomedial Hypothalamic Nucleus / physiology Feeding Behavior / physiology* Female Gastrointestinal Motility / genetics, physiology* Glucagon-Like Peptide 2 / pharmacology Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neurons / physiology* Pro-Opiomelanocortin / physiology Receptor, Melanocortin, Type 4 / genetics, physiology Receptors, Glucagon / biosynthesis, genetics, physiology* Signal Transduction / physiology |
| Grant Support | |
ID/Acronym/Agency:
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DK-075489/DK/NIDDK NIH HHS; DK-084125/DK/NIDDK NIH HHS; P30 DK-079638/DK/NIDDK NIH HHS; R01 HL051586/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/GLP-2 receptor; 0/Glucagon-Like Peptide 2; 0/MC4R protein, mouse; 0/Receptor, Melanocortin, Type 4; 0/Receptors, Glucagon; 66796-54-1/Pro-Opiomelanocortin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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