Disparate age-associated alterations in acute cortictropin effects on energy homeostasis

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DISPARATE AGE-ASSOCIATED ALTERATIONS IN ACUTE CORTICOTROPIN EFFECTS ON ENERGY HOMEOSTASIS

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.

Judit Tenk, Nóra Füredi

Department of Pathophysiology and Gerontology, Medical School, University of Pécs, Pécs, Hungary

INTRODUCTION

In the background of age-related obesity and the cachexia of aging complex age-related alterations in the catabolic [anorexigenic, food intake (FI) reducing, metabolic rate (MR) enhancing] and anabolic (FI enhancing, MR- reducing) peptide systems are assumed. Corticotropin- releasing factor (CRF) is an important central catabolic mediator. Our previous studies revealed age-related shifts in the responsiveness to an intracerebroventricular (ICV) CRF infusion in rats: anorexigenic effects were especially pronounced in the oldest, hypermetabolic response was detected in the youngest and oldest rats. Middle-aged rats did not show catabolic responsiveness to CRF. Responsiveness to acute central melanocortin agonist- and acute peripheral cholecystokinin (CCK) administration on energy homeostasis show similar age-related patterns. Other catabolic effects (e.g. those of ICV CCK injection) continuously decrease with aging.

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

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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

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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

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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, SROP-4.2.3.-12/KONV Supporting Scientific Training of Talented Youth at the University of Pécs

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