Epidemiological data suggest that body mass index and obesity are strong risk factors
for depression and anxiety. However, it is difficult to separate cause from effect,
as predisposition to obesity may enhance susceptibility to anxiety, or vice versa.
Here, we examined the effect of diet and obesity on anxiety-like behaviors in male
and female selectively bred obesity-prone and obesity-resistant rats, and outbred
Sprague-Dawley rats. We found that when obesity-prone and obesity-resistant rats do
not differ in weight or fat mass, measures of anxiety-like behavior in the elevated
plus maze and open field are similar between the two groups. However, once weight
and fat mass diverge, group differences emerge, with greater anxiety in obesity-prone
relative to obesity-resistant rats. This same pattern was observed for males and females.
Interestingly, even when obesity-resistant rats were “forced” to gain fat mass comparable
to obesity-prone rats (via prolonged access to 60% high-fat diet), anxiety-like behaviors
did not differ from lean chow fed controls. In addition, a positive correlation between
anxiety-like behaviors and adiposity were observed in male but not in female obesity-prone
rats. Finally, diet-induced weight gain in and of itself was not sufficient to increase
measures of anxiety in outbred male rats. Together, these data suggest that interactions
between susceptibility to obesity and physiological alterations accompanying weight
gain may contribute to the development of enhanced anxiety.