GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility

  • Xinfu Guan
    Department of Pediatrics, US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas;
  • Xuemei Shi
    Department of Pediatrics, US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas;
  • Xiaojie Li
    Department of Pediatrics, US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas;
  • Benny Chang
    Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas; and
  • Yi Wang
    Department of Pediatrics, US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Houston, Texas;
  • Depei Li
    Department of Critical Care, University of Texas MD Anderson Cancer Center, Houston, Texas
  • Lawrence Chan
    Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas; and

抄録

<jats:p>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 [<jats:sup>13</jats:sup>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.</jats:p>

収録刊行物

被引用文献 (1)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ