Age-related pattern of acute effects of corticotropin-releasing factor on energy balance

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AGE-RELATED PATTERN OF ACUTE EFFECTS OF

CORTICOTROPIN-RELEASING FACTOR ON ENERGY BALANCE

RESULTS AND DISCUSSION

1. Acute ICV CRF injection suppressed FI and increased MR and Tc.

2. In males both anorexigenic and hypermetabolic effects declined with aging. (Figs. 1,3)

3. Females showed significant anorexigenic responsiveness in all age- groups. (Fig. 2)

4. Age-related alterations in the responsiveness of male rats to central ICV CRF were similar to those of ICV CCK injections.

5. In the background of gender differences variations in body weight/body composition and endocrine factors (e.g. anorexigenic estrogen effects) may be assumed.

Marta Balasko, Judit Tenk, Ildiko Rostas, Margit Gaspar-Koncsecsko, Szilvia Soos, Miklos Szekely, Erika Petervari Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Pécs, Hungary

INTRODUCTION

Two main trends are observed during long-term regulation of body weight (BW): obesity of the middle-aged and aging anorexia. These trends also appear in mammals, so complex age-related alterations in the balance between catabolic and anabolic peptide systems are also assumed in the background. Catabolic corticotropin-releasing factor (CRF) is a hypothalamic downstream mediator of the melanocortin (MC) system. Effects of centrally applied MC agonists showed age-related shifts: strong anorexigenic effects in young adult and old

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weak responses in juvenile and middle-aged rats. Catabolic effects of an intracerebroventricular (ICV) CRF infusion also showed similar age- related shifts: anorexia in the young adult and old, some hypermetabolic responses in all age-groups. Middle-aged rats failed to lose BW. In this study we analyzed the acute anorexigenic and hypermetabolic effects of CRF.

We hypothesized that anorexigenic and hypermetabolic responsiveness to acute CRF administration change with different dynamics during aging. Responsiveness of young adult, younger and older middle-aged, aging and old (aged 3, 6 and 12, 18 and 14 months, respectively) male and female Wistar rats to acute ICV CRF injections (0.3 ug) was analyzed regarding parameters of energy balance. Anorexigenic effects were tested in an automated FeedScale system during 120-min re- feeding following 24-h fasting. Oxygen consumption (MR) was measured by indirect calorimetry (Oxymax). Colon (Tc) and tail skin temperatures (Ts, indicating heat loss) were recorded by thermocouples.

For statistical analysis of the data repeated-measures ANOVA was used.

METHODS AIMS

centrally applied acute CRF injections were analyzed.

In the present study age-related alterations in the responsiveness to

DVO₂ (kcal/min)

-10 -5 0 5 10 15

TIME (min)

-30 0 30 60 90 120

DT_s (^oC)

-4 -2 0 2 4 DT_c(^oC)

-1.0 -0.5 0.0 0.5 1.0 1.5 2.0

CRF 1 mg control

ICV injection

*

24 months male

*

-10 -5 0 5 10 15

TIME (min)

-30 0 30 60 90 120

DT_s (^oC)

-4 -2 0 2 4 DT_c(^oC)

-1.0 -0.5 0.0 0.5 1.0 1.5 2.0

CRF 1mg control

3 months male

*

-10 -5 0 5 10 15

TIME (min)

-30 0 30 60 90 120

DT_s (^oC)

-4 -2 0 2 4 DT_c(^oC)

-1.0 -0.5 0.0 0.5 1.0 1.5 2.0

ICV

injection6 months male

TIME (min)

0 30 60 90 120 150 180

FI (g)

0 2 4 6 8 10

ICV INJECTION

CRF 0.3 mg BW=270+ 11 control BW=271+ 8

*

18 months female

TIME (min)

0 30 60 90 120 150 180

FI (g)

0 2 4 6 8 10

ICV INJECTION

CRF 0.3 mg BW=263+ 23 conrtol BW=269+ 5

*

TIME (min)

0 30 60 90 120 150 180

FI (g)

0 2 4 6 8 10

ICV INJECTION

*

3 months female ^{CRF 0.3 m}_{control BW}^g^BW_{=218+ 5}^{=201+ 4}

TIME (min)

0 30 60 90 120 150 180

FI (g)

0 2 4 6 8 10

ICV INJECTION

24 months male

TIME (min)

0 30 60 90 120 150 180

FI (g)

0 2 4 6 8 10

ICV INJECTION

18 months male

TIME (min)

0 30 60 90 120 150 180

FI (g)

0 2 4 6 8 10

ICV INJECTION

*

12 months male

TIME (min)

0 30 60 90 120 150 180

FI (g)

0 2 4 6 8 10

ICV INJECTION

*

3 months male

Fig. 1 A-D The effects of acute ICV CRF injection on re-feeding food intake following 24-h fasting (FI) in different age-groups of male rats. Asterisks indicate significant differences.

Fig. 2 A-D

food intake following 24-h fasting (FI) in different age-groups of female rats. Asterisks indicate significant differences.

The effects of acute ICV CRF injection on re-feeding

Fig. 3 A-D The effects of acute ICV CRF injection on core temperature (Tc), oxygen consumption (VO ) and tail skin temperature ₂ (Ts) in different age-groups of male rats.

Supported by SROP-4.2.1/B-10/2/KONV-2010-0002, SROP-4.2.2./B- 10/1-2010-0029

TIME (min)

0 30 60 90 120 150 180

FI (g)

0 2 4 6 8 10

ICV INJECTION

*

-10 -5 0 5 10 15

TIME (min)

-30 0 30 60 90 120

DT_s (^oC)

-4 -2 0 2 4 DT_c(^oC)

-1.0 -0.5 0.0 0.5 1.0 1.5 2.0

12 months male

* A

C

B

D

A

C D

B

C D A B