Aims: 

Long-term body weight (BW) regulation shows two major trends: fat accumulation in middle-aged, followed by anorexia of aged populations with loss of active tissues, leading to sarcopenia. In the background, age-related shifts in the peripheral and central catabolic and anabolic peptide systems may be assumed. Our previous results show complex age-related shifts in the responsiveness of the central catabolic melanocortin system with diminished sensitivity in middle-aged and high efficacy in old rats. In the present study we analyzed age-related alterations in the responsiveness of central anabolic neuropeptide Y (NPY) and those of the peripheral catabolic cholecystokinin (CCK) system.

Methods: 

Food intake (FI) and BW of juvenile (2-month), young adult (3–4-month), middle-aged (6- and 12-month) and aged (24-month) male Wistar rats were recorded following an acute intracerebroventricular injection of 0, 5 mg NPY or an intraperitoneal injection of 0, 5 mg CCK. Orexigenic NPY was used to induce FI (measured for 3-h and expressed as % of usual daily FI) in non-fasted rats. Anorexigenic CCK was tested on the 3-h re-feeding period following 48-h fasting. All test sessions started at 9.00 a.m.

Results: 

Central administration of anabolic NPY induced significant FI in juvenile, had weaker orexigenic response in young adult rats, very pronounced one in middle-aged but strongly declining effects in aged animals. Responsiveness to catabolic CCK also exhibited a characteristic pattern: weak responsiveness in juvenile, a strong one in young adult, absence of significant effects in middle-aged and very pronounced anorexia in old rats. This latter age-related pattern was similar to that exhibited by central melanocortins.

Conclusions: 

The FI-associated effects of regulatory peptides involved in energy homeostasis show age-related alterations that appear to contribute to the explanation of the obesity in middle-aged rats as well as of the cachexia and sarcopenia in old animals. (OTKA PD-84241, PTE AOK-KA-34039-02/2010)