High-Intensity Interval Training Ameliorates High-Fat Diet-Induced Cognitive Impairment and Is Associated with Altered Adipokine Signaling in the Olfactory Bulb and Hippocampus.

High-fat diets have become increasingly common, but their negative impact on cognitive health is of growing concern. Such diets are associated with deficits in spatial learning and memory, particularly impacting brain regions such as the olfactory bulb (OB) and hippocampus (HPC). We investigated the benefits of high-intensity interval training (HIIT) on high-fat diet-induced deficits in spatial learning and memory, focusing on the OB and HPC. Eighteen C57BL/6 mice were divided into three groups (n = 6 per group): (1) normal control (NC), (2) high-fat diet (HFD), and (3) HFD with HIIT training (HFD + HIIT). The HFD groups were fed a 60% HFD for 12 weeks, after which mice in the HFD + HIIT group underwent 8 weeks of HIIT (5 days per week). The Barnes maze test was conducted during the last week of HIIT, and tissue levels of leptin, adiponectin, and their receptors in the OB and HPC were then measured. Consumption of a HFD decreased cell counts (OB: p = 0.001; HPC: p = 0.01), adiponectin levels (OB: p = 0.0002; HPC: p = 0.018), and adiponectin receptors in both the OB and HPC (OB: p = 0.0003; HPC: p = 0.052). In contrast, a HFD increased leptin levels and its receptors in both the OB and HPC (OB: p < 0.0001, p < 0.0001; HPC: p = 0.0003, p = 0.003, respectively), resulting in detrimental effects on spatial learning and memory. These effects of HFD were partially reversed by HIIT (p < 0.05). These findings identify the OB as a previously underexplored brain region that exhibits adipokine-related adaptations following HIIT and is associated with improvements in spatial memory in HFD-fed mice. Further mechanistic studies are needed to determine whether OB signaling directly contributes to these cognitive effects.