The aim of this study was to investigate the long-term neurochemical alterations in the hippocampus of mice fed a high-fat diet (HFD) while plasma leptin and corticosterone levels were monitored. Although metabolic disturbances induced by the excess intake of fat are assumed to cause depression, the relationship underlying dysfunctional adipose tissue, stress hormone release, and excitatory metabolism has not been fully understood yet.

Four-week-old male C57BL/6 mice were separated into a HFD-fed group (n = 8) and low-fat diet-fed group (n = 8). Proton magnetic resonance spectroscopy was used to measure the long-term changes in neurochemicals in the hippocampus at 0, 5, and 10 weeks and blood samples were taken at the same time to assess plasma hormones levels. At the end of the experiment, magnetic resonance imaging was performed to quantify abdominal fat accumulation.

At 10 weeks, corticosterone and leptin levels were significantly increased in the HFD group compared with the low-fat diet group. In addition, aspartate, glutamate, total choline, and N-acetylaspartic acid levels were significantly increased, but glutamine/glutamate ratios were substantially decreased at 10 weeks in the HFD group. These results were compatible with HFD-induced acute stress responses and changes in N-methyl-d-aspartate receptor-induced plasticity.

These findings demonstrated that the long-term ingestion of a HFD induced hyperglutamatergic metabolism and altered glutamine-glutamate cycling. Therfore, it is suggested that hypothalamic-pituitary-adrenal dysfunction and hyperglutamatergic activation in the hippocampus resulting from the HFD.

这项研究的目的是调查高脂饮食（HFD）小鼠的海马中长期神经化学变化，同时监测血浆瘦素和皮质酮水平。尽管认为由过量摄入脂肪引起的代谢紊乱会导致抑郁，但尚未完全了解脂肪组织功能紊乱，应激激素释放和兴奋性代谢之间的关系。

将四周大的雄性C57BL / 6小鼠分为HFD喂养组（n = 8）和低脂饮食喂养组（n = 8）。质子磁共振波谱用于测量0、5和10周时海马神经化学物质的长期变化，并同时采集血样以评估血浆激素水平。实验结束时，进行磁共振成像以量化腹部脂肪堆积。

与低脂饮食组相比，HFD组在10周时的皮质酮和瘦素水平显着增加。此外，HFD组在第10周时，天冬氨酸，谷氨酸，总胆碱和N-乙酰天门冬氨酸的含量显着增加，但谷氨酰胺/谷氨酸的比率却显着降低。这些结果与HFD诱导的急性应激反应和变化在N-甲基兼容d天冬氨酸受体诱导的可塑性。

这些发现表明，长期摄入HFD会引起高谷氨酸能代谢并改变谷氨酰胺-谷氨酸循环。因此，提示HFD引起海马下丘脑-垂体-肾上腺功能障碍和谷氨酸过高活化。