title: Hindbrain ghrelin receptor signaling is sufficient to maintain fasting glucose.
abstract: The neuronal coordination of metabolic homeostasis requires the integration of hormonal signals with multiple interrelated central neuronal circuits to produce appropriate levels of food intake, energy expenditure and fuel availability. Ghrelin, a peripherally produced peptide hormone, circulates at high concentrations during nutrient scarcity. Ghrelin promotes food intake, an action lost in ghrelin receptor null mice and also helps maintain fasting blood glucose levels, ensuring an adequate supply of nutrients to the central nervous system. To better understand mechanisms of ghrelin action, we have examined the roles of ghrelin receptor (GHSR) expression in the mouse hindbrain. Notably, selective hindbrain ghrelin receptor expression was not sufficient to restore ghrelin-stimulated food intake. In contrast, the lowered fasting blood glucose levels observed in ghrelin receptor-deficient mice were returned to wild-type levels by selective re-expression of the ghrelin receptor in the hindbrain. Our results demonstrate the distributed nature of the neurons mediating ghrelin action.
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Scott
authors.forename: Mario
authors.initials: M
authors.lastname: Perello
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Chuang
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakata
authors.forename: Laurent
authors.initials: L
authors.lastname: Gautron
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Lee
authors.forename: Danielle
authors.initials: D
authors.lastname: Lauzon
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Zigman
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D005215:Fasting / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000378:metabolism; D007003:Hypoglycemia / Q000097:blood / Q000235:genetics / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D008297:Male; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D018398:Homeodomain Proteins; C109220:NBPhox protein; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D014157:Transcription Factors; C045073:Cre recombinase; D019426:Integrases