title: Age versus nutritional state in the development of central leptin resistance.
abstract: Leptin, a catabolic adiposity signal acts in the hypothalamus via suppressing food intake and inducing hypermetabolism. Age and obesity are accompanied by leptin resistance. The present study aimed to clarify which components of the catabolic leptin effects are influenced most strongly by aging and which ones by nutritional state-induced alterations in body composition. In our biotelemetric study the effects of a 7-day intracerebroventricular leptin infusion on various parameters of energy balance (food intake, body weight, oxygen consumption, heart rate and body temperature) were analyzed in male Wistar rats of different age-groups (from 3 to 24 months) and nutritional states (normally fed, diet-induced obese and calorie-restricted). Leptin resistance of older animals affected hypermetabolic actions, whereas leptin induced anorexia in all age-groups. Weight reducing effect of leptin diminished in middle-aged and aging animals to become significant again in the oldest group. In diet-induced obese rats leptin-induced hypermetabolism of the young rats and hypermetabolism plus anorexia of the aging ones were suppressed. Calorie-restriction reduced body weight and fat mass to a similar extent in all age-groups. It strongly enhanced leptin-induced hypermetabolism at all ages and prevented the manifestation of anorexigenic actions of leptin with the exception of the oldest group. This latter finding suggests an unexpected increase of responsiveness to anorexigenic leptin actions in old rats. Accordingly, anorexia and hypermetabolism change in disparate ways with aging. Nutritional state predominantly influences hypermetabolic leptin actions. Resistance to both hypermetabolic and anorexigenic actions were promoted by obesity, while calorie-restriction enhanced responsiveness to leptin, especially in old rats.
authors.affiliation: Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary, 12. Szigeti str., H-7624 Pécs, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Pétervári
authors.affiliation: Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary, 12. Szigeti str., H-7624 Pécs, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Rostás
authors.affiliation: Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary, 12. Szigeti str., H-7624 Pécs, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Soós
authors.affiliation: Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary, 12. Szigeti str., H-7624 Pécs, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Tenk
authors.affiliation: Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary, 12. Szigeti str., H-7624 Pécs, Hungary.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mikó
authors.affiliation: Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary, 12. Szigeti str., H-7624 Pécs, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Füredi
authors.affiliation: Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary, 12. Szigeti str., H-7624 Pécs, Hungary. Electronic address: miklos.szekely@aok.pte.hu.
authors.forename: Miklós
authors.initials: M
authors.lastname: Székely
authors.affiliation: Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Hungary, 12. Szigeti str., H-7624 Pécs, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Balaskó
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D031204:Caloric Restriction; D004734:Energy Metabolism / Q000187:drug effects; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020738:Leptin
keywords: Aging; Calorie-restriction; Energy balance; Leptin; Obesity