title: Neuronal Deletion of Ghrelin Receptor Almost Completely Prevents Diet-Induced Obesity.
abstract: Ghrelin signaling has major effects on energy and glucose homeostasis, but it is unknown whether ghrelin's functions are centrally and/or peripherally mediated. The ghrelin receptor, growth hormone secretagogue receptor (GHS-R), is highly expressed in the brain and detectable in some peripheral tissues. To understand the roles of neuronal GHS-R, we generated a mouse line where Ghsr gene is deleted in all neurons using synapsin 1 (Syn1)-Cre driver. Our data showed that neuronal Ghsr deletion abolishes ghrelin-induced spontaneous food intake but has no effect on total energy intake. Remarkably, neuronal Ghsr deletion almost completely prevented diet-induced obesity (DIO) and significantly improved insulin sensitivity. The neuronal Ghsr-deleted mice also showed improved metabolic flexibility, indicative of better adaption to different fuels. In addition, gene expression analysis suggested that hypothalamus and/or midbrain might be the sites that mediate the effects of GHS-R in thermogenesis and physical activity, respectively. Collectively, our results indicate that neuronal GHS-R is a crucial regulator of energy metabolism and a key mediator of DIO. Neuronal Ghsr deletion protects against DIO by regulating energy expenditure, not by energy intake. These novel findings suggest that suppressing central ghrelin signaling may serve as a unique antiobesity strategy.
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
authors.forename: Ligen
authors.initials: L
authors.lastname: Lin
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Pingwen
authors.initials: P
authors.lastname: Xu
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Kenji
authors.initials: K
authors.lastname: Saito
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX Division of Endocrinology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wei
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Adelina G
authors.initials: AG
authors.lastname: Meadows
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Odelia Y N
authors.initials: OY
authors.lastname: Bongmba
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Geetali
authors.initials: G
authors.lastname: Pradhan
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, TX.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX Huffington Center on Aging, Baylor College of Medicine, Houston, TX Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX Department of Nutrition and Food Science, Texas A&M University, College Station, TX yuxiangs@tamu.edu.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002153:Calorimetry, Indirect; D059305:Diet, High-Fat / Q000009:adverse effects*; D004435:Eating / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005260:Female; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D060888:Real-Time Polymerase Chain Reaction; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology
chemical_list: D054440:Receptors, Ghrelin; D016704:Synapsins