title: Role of hypothalamic neuropeptide Y and orexigenic peptides in anorexia associated with experimental colitis in the rat.
abstract: Neuropeptide Y (NPY) is thought to play a crucial role in the normal hypothalamic response to starvation. After a period of food restriction, increased release of NPY induces hunger and hyperphagia, and helps to restore body weight to its set point. Persistent anorexia in rats with experimental colitis implies failure of this adaptive feeding response. In vivo NPY release and regional hypothalamic NPY concentrations were measured in rats with trinitrobenzenesulphonic acid (TNBS)-induced colitis, healthy controls and animals pair-fed to match the food intake of the colitic group. Food intake in the colitic group was assessed after administration of NPY and two other potent orexigenic peptides: melanin-concentrating hormone (MCH) and hypocretin (orexin-A). Food intake was decreased by 30-80% below control values for 5 days in the colitic rats. In both the pair-fed and colitic groups, release of NPY in the paraventricular nucleus was significantly increased compared with free-feeding controls. Intraventricular or intrahypothalamic administration of NPY, MCH or hypocretin elicited a feeding response in healthy controls, but not in the colitic group. In summary, animals with TNBS-colitis and anorexia show an appropriate increase in hypothalamic NPYergic activity. However, the failure of NPY and other orexigenic peptides to increase feeding in the colitic group indicates suppression of feeding, either by inhibition of a common downstream hypothalamic neuronal pathway or by induction of one or more potent anorexigenic agents.
authors.affiliation: Digestive Diseases Research Centre, St Bartholomew's and The Royal London School of Medicine & Dentistry, 2 Newark Street, London E1 2AT, UK. a.b.ballinger@mds.qmw.ac.uk
authors.forename: A B
authors.initials: AB
authors.lastname: Ballinger
authors.forename: G
authors.initials: G
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Corder
authors.forename: T
authors.initials: T
authors.lastname: El-Haj
authors.forename: M J
authors.initials: MJ
authors.lastname: Farthing
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D000855:Anorexia / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007028:Hypothalamic Hormones / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008543:Melanins / Q000494:pharmacology; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology; D000068797:Orexins; D010907:Pituitary Hormones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D007028:Hypothalamic Hormones; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D014302:Trinitrobenzenesulfonic Acid; D003345:Corticosterone