title: Age-related changes in central effects of corticotropin-releasing factor (CRF) suggest a role for this mediator in aging anorexia and cachexia.
abstract: Hypothalamic corticotropin-releasing factor (CRF) lays downstream to catabolic melanocortins and at least partly mediates their catabolic effects. Age-related changes in the melanocortin system (weak responsiveness in middle-aged and a strong one in old rats) have been shown to contribute to middle-aged obesity and later to aging anorexia and cachexia of old age groups. We hypothesized that catabolic (anorexigenic and hypermetabolic) CRF effects vary with aging similarly to those of melanocortins. Thus, we aimed to test whether age-related variations of CRF effects may also contribute to middle-aged obesity and aging anorexia leading to weight loss of old age groups. Food intake, body weight, core temperature, heart rate, and activity were recorded in male Wistar rats of young, middle-aged, aging, and old age groups (from 3 to 24 months) during a 7-day intracerebroventricular CRF infusion (0.2 μg/μl/h) in a biotelemetric system. In addition, CRF gene expression was also assessed by quantitative RT-PCR in the paraventricular nucleus (PVN) of intact animals of the same age groups. The infusion suppressed body weight in the young, aging, and old rats, but not in middle-aged animals. Weak anorexigenic and hypermetabolic effects were detected in the young, whereas strong anorexia (without hypermetabolism) developed in the oldest age groups in which post mortem analysis showed also a reduction of retroperitoneal fat mass. CRF gene expression in the PVN increased with aging. Our results support the potential contribution of age-related changes in CRF effects to aging anorexia and cachexia. The role of the peptide in middle-aged obesity cannot be confirmed.
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Tenk
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Rostás
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Füredi
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mikó
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Margit
authors.initials: M
authors.lastname: Solymár
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Soós
authors.affiliation: Department of Anatomy, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gaszner
authors.affiliation: Department of Pharmaceutical Biotechnology, Medical School, University of Pecs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Diana
authors.initials: D
authors.lastname: Feller
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Székely
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Pétervári
authors.affiliation: Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti str, Pécs, H-7624, Hungary. marta.balasko@aok.pte.hu.
authors.forename: Márta
authors.initials: M
authors.lastname: Balaskó
mesh_terms: D000367:Age Factors; D000375:Aging / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D000855:Anorexia / Q000378:metabolism* / Q000503:physiopathology; D001835:Body Weight; D002100:Cachexia / Q000378:metabolism* / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D007263:Infusions, Parenteral; D020738:Leptin / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D020738:Leptin; D012313:RNA; D003346:Corticotropin-Releasing Hormone
keywords: Aging; Core temperature; Corticotropin-releasing factor (CRF); Energy homeostasis; Food intake; Wistar rat