Anorexic effect of peripheral cholecystokinin (CCK) varies with age and body composition (Short communication)

Abstract

Obesity of middle-aged mammals is followed at old age by anorexia and cachexia leading to sarcopenia. Complex age- and body composition-related alterations in the regulation of energy homeostasis may be assumed in the background. We aimed to test the possible contribution of age- and body composition-related changes of satiety responses to catabolic brain-gut-axis peptide cholecystokinin (CCK) to these alterations in energy balance during aging. Male Wistar rats (6-8 animals/group) aged 2 months (juvenile), 3 months (young adult), 6 or 12 months (early or late middle-aged), and 24 months (old) were injected intraperitoneally with 5 μg CCK-8 prior to re-feeding after 48-h food-deprivation. CCK suppressed re-feeding in young adult (26.8%), early middle-aged (35.5%), and old (31.4%) animals, but not in juvenile or late middle-aged rats (one-way ANOVA). CCK-resistance of 12 months old rats was prevented by life-long calorie-restriction: CCK suppressed their re-feeding by 46.8%. Conversely, in highfat diet-induced obese 6 months old rats CCK failed to suppress re-feeding. In conclusion, age-related changes in satiety responsiveness to CCK may contribute to the age-related obesity of middle-aged as well as to the anorexia of old animals. CCK-responsiveness is also influenced by body composition: calorie-restriction prevents the resistance to CCK, pre-existing obesity enhances it.

Mechanism of Action of Acupuncture in Obesity: A Perspective From the Hypothalamus

“…Cholecystokinin (CCK), originates from the gastrointestinal (GI) tract, is transmitted from peripheral to the NTS via the vagus nerve. Satiety signal of CCK in NTS may integrate with the hypothalamic inputs implicated in food regulation, and its activation in the NTS results in decreased food intake and weight loss and eventually results in anorexia (139,140). CCK has been known to be a key satiety signal and exert inhibitory actions on food intake in rodents (141).…”

Stability of CART peptide expression in the nucleus accumbens in aging

“…the age-related alteration of cholecystokinin (CCK) sensitivity was shown throughout the lifespan: a declination of its anorexic effect was observed with age, with a consequent elevation of CCK plasma level [4,5]. an age-dependent effect was also observed by administration of another anorexigenic neuropeptide, the alpha-melanocyte-stimulating hormone.…”