High-fat diet-induced hyperglutamatergic activation of the hippocampus in mice: A proton magnetic resonance spectroscopy study at 9.4T.

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.