Exercise Training Rescues High Fat Diet-induced Neuronal Nitric Oxide Synthase Expression In Hippocampus And Cortex: 1110 Board #289 May 31 2

Western high-fat diet (HFD) consumption and being overweight induce hippocampal atrophy and deterioration of function. These alterations are associated with mental disorders, such as depression and anxiety. Exercise is an effective therapeutic treatment to combat obesity and enhance brain health. Numerous studies have demonstrated that neuronal nitric oxide synthase (nNOS) is a key regulator of affective behavior. Increased nNOS expression leads to anxiety, while reduced brain nNOS in an enriched environment that includes running exercise has anxiolytic effects. PURPOSE: We investigated whether HFD consumption and exercise training altered nNOS expression in the brain. METHODS: Twenty 4-week-old male C57BL/6J mice were used. After 2 weeks of acclimatization, mice were randomly assigned to a standard diet (SD; n = 5) or HFD group (n = 15). After 6 weeks, HFD-fed mice were further divided into either a non-exercise (HFD; n = 7) or a HFD (12 weeks) with exercise group (HFD+Ex; n = 8). The HFD+Ex group was allowed free access to a running wheel. Western blotting was performed to determine nNOS protein expression levels in the hippocampus (Hp), cortex (Cx) and cerebellum (Ce) from SD, HFD and HFD+Ex mice. RESULTS: Body weights were significantly increased in HFD-fed mice (SD: 26.0 ± 0.4 g; HFD: 36.6 ± 1.5 g; HFD+Ex: 29.1 ± 0.5 g; p < 0.01). Similarly, mesenteric fat weights were increased in the HFD group, while exercise training mitigated this effect (SD: 0.16 ± 0.04 g; HFD: 0.56 ± 0.10; HFD+Ex: 0.25 ± 0.03; p < 0.01). Compared with that of SD mice, Hp and Cx nNOS expression levels increased significantly with HFD feeding (Hp: 1.90 ± 0.28 fold increase, p < 0.05; Cx: 1.89 ± 0.49; p < 0.01). HFD-induced Hp and Cx nNOS expression was reduced in HFD+Ex mice to levels comparable to those of the SD group, though the difference in the Cx was not significant (Hp: 0.86 ± 0.16 fold increase, Cx: 1.48 ± 0.22; p = 0.1003). While Hp and Cx nNOS expression levels were susceptible to HFD consumption and exercise, those in the Ce were unchanged (p > 0.05). CONCLUSION: We conclude that exercise training restores HFD-induced nNOS expression in the Hp and Cx. Our results indicate that HFD-induced brain dysfunction is regulated by nNOS in the Hp and Cx, and exercise has therapeutic potential for mitigating HFD-induced depression and anxiety via the nNOS/NO pathway.