Anxiety-like behaviors and hippocampal nNOS in response to diet-induced obesity combined with exercise.

A high-fat diet (HFD) and overweight status can induce hippocampal dysfunction, leading to depression and anxiety. Exercise has beneficial effects on emotional behaviors. We previously reported that exercise training rescues HFD-induced excess hippocampal neuronal nitric oxide synthase (nNOS) expression, which is a key regulator of anxiety. Here, we investigated anxiety-like behaviors and hippocampal nNOS expression in response to HFD combined with exercise. Mice were assigned to standard diet, HFD, or HFD with exercise groups for 12 weeks. We found that exercise during the final 6 weeks of the HFD regime improved 12 weeks of HFD-induced defecation, accompanied by rescue of excess nNOS expression. However, anxiety indicators in the elevated plus maze were unchanged. These effects were not apparent after only 1 week of exercise. In conclusion, 6 weeks of exercise training reduced HFD-related anxiety according to one of our measures (defecation), and reversed changes in the hippocampal nNOS/NO pathway.