Journal
EXPERIMENTAL GERONTOLOGY
Volume 48, Issue 11, Pages 1180-1188Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2013.07.006
Keywords
Aging; Food intake; Metabolic rate; Cholecystokinin; Obesity; Calorie-restriction
Categories
Funding
- Hungarian Agency for Scientific [OTKA PD-84241]
- University of Pecs [34039/KA-OTKA/13-02, 34039/KA-2013/13-25]
- EU
- Hungarian State TAMOP [SROP-4.2.2/B-10/1-2010-0029, SROP-4.2.1.B-10/2/KONV-2010-0002, SROP-4.2.2.A-11/1/KONV-2012-0024, SROP 4.2.4.A/2-11-1-2012-0001]
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Cholecystokinin (CCK) is anorexic, irrespective whether it is applied intraperitoneally (IP) or intracerebroventricularly (ICV) in male Wistar rats. The metabolic effects depend on the route of administration: by the IP route it elicits hypothermia (presumably by type-1 receptors, CCK1R-s), while ICV administration is followed by fever-like hypermetabolism and hyperthermia via activation of CCK2R-s, which latter response seems to be most important in the postprandial (compensatory) hypermetabolism. The efficacy of the IP injected CCK varies with age: it causes strong anorexia in young adult 4 and 6-months old and again in old rats (aged 1824 months), but the middle-aged (12-month old) ones seem to be resistant to this effect. Such pattern of effects may contribute to the explanation of age-related obesity observed in middle-aged animals as well as to the aging anorexia and loss of body weight in old ones. Diet-induced obesity accelerates the appearance of CCK-resistance as well as the return of high sensitivity to CCK in further aging, while chronic calorie-restriction prevents the development of resistance, as if the speed of the age-related regulatory changes was altered by the nutritional state. The effects of ICV applied CCK also change with age: the characteristic anorexic and hypermetabolic/hyperthermic effects can be observed in young adult rats, but the effects gradually and monotonically decline with age and disappear by the old age of 24 months. These disparate age-related patterns of CCK efficacy upon peripheral or central administration routes may indicate that although both peripheral and central CCKR-s exert anorexic effects, they may have dissimilar roles in the regulation of overall energy balance. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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