Investigation of Behavior and Plasma Levels of Corticosterone in Restrictive- and Ad Libitum-Fed Diet-Induced Obese Mice

Abstract

Diet-induced obesity (DIO) mice models are commonly used to investigate obesity-related health problems. Until now, only sparse data exist on the influence of DIO on behavior and stress hormones in mice. The present study investigates high-fat DIO with two different feeding regimes on behavioral parameters in mice. Various behavioral tests (open field, elevated plus maze, social interaction, hotplate) were performed with female BALB/c and male C57BL/6 mice after a feeding period of twelve weeks (restrictive vs. ad libitum and normal-fat diet vs. high-fat diet) to investigate levels of anxiety and aggression. BALB/c mice were DIO-resistant and therefore the prerequisite for the behavior analyses was not attained. C57BL/6 mice fed a high-fat diet had a significantly higher body weight and fat mass compared to C57BL/6 mice fed a control diet. Interestingly, the DIO C57BL/6 mice showed no changes in their aggression- or anxiety-related behavior but showed a significant change in the anxiety index. This was probably due to a lower activity level, as other ethological parameters did not show an altered anxiety-related behavior. In the ad libitum-fed DIO group, the highest corticosterone level was detected. Changes due to the feeding regime (restrictive vs. ad libitum) were not observed. These results provide a possible hint to a bias in the investigation of DIO-related health problems in laboratory animal experiments, which may be influenced by the lower activity level.

Keywords: activity; aggression; anxiety; behavior; mice; obesity.

Figure 1

Timeline.

Figure 2

(A) Final body weights in BALB/c mice. (B) Body weight gain in BALB/c mice. (C) Visceral fat mass in BALB/c mice. (D) Final body weights in C57BL/6 mice. (E) Body weight gain in C57BL/6 mice. (F) Visceral fat mass in C57BL/6 mice. g = gram, adlib = ad libitum, res = restrictive, con = normal weight DIO = diet-induced obesity. Means ± standard error of mean (SEM), * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001.

Figure 3

(A) Open-field test with C57BL/6 mice, control = normal weight, DIO = diet-induced obesity, means ± standard error of mean (SEM), ** p ≤ 0.01, *** p ≤ 0.001. (B) Anxiety index (center distance/total distance ratio) of C57BL/6 mice, control = normal weight, DIO = diet-induced obesity, means ± standard error of mean (SEM), * = p ≤ 0.05. (C) Open-field test with C57BL/6 mice. (D) Anxiety index (center distance/total distance ratio) of C57BL/6 mice.

Figure 4

(A) Elevated plus maze test with C57BL/6 mice, control = normal weight, DIO = diet-induced obesity, means ± standard error of mean (SEM), * p ≤ 0.05, ** p ≤ 0.01. (B) Elevated plus maze test with C57BL/6 mice, means ± standard error of mean (SEM).

Figure 5

Hotplate test with C57BL/6 mice. DIO = diet-induced obesity, means ± standard error of mean (SEM).

Figure 6

Plasma corticosterone levels in C57BL/6 mice. DIO = diet-induced obesity, means ± standard error of mean (SEM).