NÓRA FÜREDI, ILDIKÓ ROSTÁS, JUDIT TENK, ALEXANDRA MIKÓ
DEPARTMENT OF PATHOPHYSIOLOGY AND GERONTOLOGY, MEDICAL SCHOOL, UNIVERSITY OF PÉCS, HUNGARY
INTRODUCTION
During aging, two major trends are observed in the regulation of body weight and body composition: aging obesity is followed later by aging anorexia and sarcopenia. Complex age- and body composition-related alterations in the regulation of energy homeostasis may be assumed in the background. Our previous studies revealed well-defined age-related shifts in the responsiveness to peptide mediators of energy balance (such as the central catabolic melanocortin system) that may contribute to the explanation of both age-related trends. It was also shown that body composition also exerts significant influence on the function of regulatory peptides. Cholecystokinin (CCK), a major catabolic peptide of the brain-gut axis, has long been known to induce satiety by activating peripheral (vagal) CCK type 1 receptors. Changes in the responsiveness to CCK possibly contribute to alterations in energy balance during aging.
AIMS
Our aim was to study age- and body composition-related alterations in the anorexigenic responsiveness of rats to peripheral CCK.
METHODS
Male Wistar rats aged 2-, 4-, 6 - or 12- 18- and 24 months (juvenile, young adult, early or late middle-aged, aging and old, respectively) were injected by CCK intraperitoneally (IP) at an 5 µg dose to test anorexigenic effects of CCK on short- term (3-h) re-feeding following 48-h fasting. Controls were injected with pyrogen free saline (PFS). Twelve-month-old calorie-restricted (40% reduction, CR) and 6- or 12-month-old high-fat diet-induced obese (60% fat calories, HF) groups were also established. Food intake (FI) was recorded in automated FeedScale system (Columbus). Body weight was measured manually every day. For statistical analysis one-way ANOVA test was performed.
RESULTS
1. The anorexic effects of peripherally administered CCK showed well-defined age-related shifts.
2. CCK suppressed re-feeding in young adult, early middle-aged and old animals.
3. CCK-resistance of late middle-aged rats was prevented by life-long calorie- restriction.
4. In obese rats the CCK-induced suppression of re-feeding was diminished already in the early middle-aged HF6 group. HF12 on the other hand showed CCK-sensitivity similar to that of NF18.
CONCLUSION
Age-related changes in the responsiveness to CCK may contribute not only to the explanation of aging anorexia, but also to that of middle-aged obesity. CCK-responsiveness is also influenced by body composition: calorie restriction delays, obesity promotes age-related regulatory alterations.
Effect of IP CCK on the 48-h fasting-induced cumulative 3-h FI (in kJ/100g body weight) in normally fed (NF) rats aged 2, 4, 6, 12, 18 and 24 months, in high-fat diet induced obese 6- and 12-month-old rats (HF6, HF12) and in
12-month-old calorie-restricted (CR12) ones. The rate of reduction is denoted above the pairs of columns in percentage of the corresponding
control value.
SROP 4.2.4. A2-ELMH-12-0124, OTKA PD84241, SROP-4.2.1/B-10/2/KONV-2010-0002,
34039/KA-OTKA/13-02
CHOLECYSTOKININ EFFECTS ON ENERGY BALANCE DEPEND ON AGE AND BODY COMPOSITION
0 20 40 60 0 20 40
60 AGE (month)
FI (kJ/100 g body weight)
0 20 40 60
IP PFS IP CCK
27.1% 35.5%
* * *
NS NS
35.9%
7.3% 9.2%
NF4 NF6 NF12 NF24
NF2
13.7% 28.4%
NS
CR12
*
27.3%
*
NF18
HF6 HF12
46.8%
