Department of Biomedical Engineering, Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Neurochem Int. 2018 Mar;114:10-17. doi: 10.1016/j.neuint.2017.12.007. Epub 2017 Dec 21.
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.
本研究旨在探讨高脂饮食（HFD）喂养的小鼠中海马体的长期神经化学变化，同时监测其血浆瘦素和皮质酮水平。尽管人们认为过量摄入脂肪引起的代谢紊乱会导致抑郁，但脂肪组织功能障碍、应激激素释放和兴奋性代谢之间的关系尚未完全阐明。将 4 周龄雄性 C57BL/6 小鼠分为 HFD 喂养组（n=8）和低脂饮食喂养组（n=8）。采用质子磁共振波谱法测量海马体神经化学物质的长期变化，分别在 0、5 和 10 周时采集血样，以评估血浆激素水平。实验结束时，进行磁共振成像以定量腹部脂肪堆积。10 周时，HFD 组的皮质酮和瘦素水平明显高于低脂饮食组。此外，在 HFD 组中，10 周时天冬氨酸、谷氨酸、总胆碱和 N-乙酰天冬氨酸水平显著升高，但谷氨酰胺/谷氨酸比值显著降低。这些结果与 HFD 诱导的急性应激反应和 N-甲基-D-天冬氨酸受体诱导的可塑性变化一致。这些发现表明，长期摄入 HFD 会导致谷氨酸代谢亢进和谷氨酰胺-谷氨酸循环改变。因此，建议 HFD 引起的下丘脑-垂体-肾上腺功能障碍和海马体的谷氨酸能激活。
