title: Chronic overproduction of ghrelin in the hypothalamus leads to temporal increase in food intake and body weight.
abstract: Ghrelin is known to be a critical stimulator of feeding behavior mainly via actions in the hypothalamus. However, its functional contribution to the control of energy homeostasis under chronic elevated conditions is unknown. Here we show that overproduction of ghrelin via an AAV viral delivery system in the hypothalamus leads to an increase in food intake associated with increases in body weight. However, this increase in food intake is only temporary and is diminished and no longer significant after 3 weeks. Analysis of brain sections of mice 6 weeks after AAV-ghrelin virus injection demonstrates unaltered neuropeptide Y levels but strongly up-regulated pro-opiomelanocortin levels indicating that a compensatory mechanism has been activated to counter regulate the feeding stimulatory actions of ghrelin. This demonstrates that control mechanism exists that is activated under conditions of prolonged high ghrelin levels, which could potentially be utilized to control feeding and the development of obesity.
authors: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors: Y
authors: Y
authors: Qi
authors: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia; Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors: K
authors: K
authors: Inoue
authors: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors: M
authors: M
authors: Fu
authors: Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors: A
authors: A
authors: Inui
authors: Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia; School of Medical Sciences, University of NSW, NSW, Australia. Electronic address: h.herzog@garvan.org.au.
authors: H
authors: H
authors: Herzog
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000502:physiology; D000273:Adipose Tissue / Q000254:growth & development; D000818:Animals; D000229:Dependovirus / Q000235:genetics; D004435:Eating / Q000502:physiology*; D002149:Energy Intake; D005822:Genetic Vectors / Q000494:pharmacology; D054439:Ghrelin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D015430:Weight Gain / Q000502:physiology*
chemical_list: D054439:Ghrelin; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D011333:Pro-Opiomelanocortin; D000217:Acyltransferases; C526983:Mboat4 protein, mouse
keywords: Energy homeostasis; Ghrelin; Obesity