title: Ghrelin-induced hypothermia: a physiological basis but no clinical risk.
abstract: Ghrelin increases food intake and decreases energy expenditure, promoting a positive energy balance. We observed a single case of serious hypothermia during sustained ghrelin treatment in a male subject, suggesting that ghrelin may play a role in the regulation of body temperature. We therefore investigated the effect of ghrelin treatment on body temperature in rodents and humans under controlled conditions. Intriguingly, we could demonstrate ghrelin binding in axon terminals of the medial preoptic area of the hypothalamus located in the vicinity of cold-sensitive neurons. This localization of ghrelin receptors provides a potential anatomical basis for the regulation of body temperature by ghrelin. However, our follow-up studies also indicated that neither a chronic i.c.v. application of ghrelin in rats, nor a single s.c. injection under cold exposure in mice resulted in a relevant decrease in body core temperature. In addition, a four-hour intravenous ghrelin infusion did not decrease body surface temperature in healthy humans. We concluded that while there is a theoretical molecular basis for ghrelin to modify body temperature in mammals, its magnitude is irrelevant under physiologic circumstances. Hypothermia is not likely to represent a serious risk associated with this agent and pathway.
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, A.-Scheunert-Allee 114-116, D14558 Nuthetal, Germany. wiedmer@dife.de
authors.forename: Petra
authors.initials: P
authors.lastname: Wiedmer
authors.forename: Florian
authors.initials: F
authors.lastname: Strasser
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.forename: Richard
authors.initials: R
authors.lastname: Dimarchi
authors.forename: Thomas
authors.initials: T
authors.lastname: Lutz
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.forename: Jenny
authors.initials: J
authors.lastname: Tong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin / Q000494:pharmacology*; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar; D013686:Telemetry
chemical_list: D054439:Ghrelin