代謝型疾病與憂鬱症為二重要的全球性健康議題。其高共病性顯示此二疾病間有所交互作用。釐清此二疾病間之交互作用將有助於發展出，針對此二疾病患者之全人照護方針。本研究中，吾人利用高脂飲食來於實驗小鼠中誘發代謝型疾病。結果顯示，高脂飲食導致腎上腺皮質激素，例：皮質酮，之過度分泌。而此因高脂飲食所導致之皮質酮過泌，參與在高脂飲食所導致之脂肪新生當中。此外，高脂飲食亦導致小鼠表現出類憂鬱行為。相較於正常小鼠，在高脂餵養小鼠的海馬回內，其星狀膠細胞突觸之複雜程度與膠細胞麩胺酸轉運子之表現量都降低。而利用慢病毒敲落來下調膠細胞麩胺酸轉運子於海馬回中之表現量，得以在正常小鼠中誘發出類憂鬱表現。而給予高脂餵養小鼠利魯唑治療，則可回復其海馬回內膠細胞麩胺酸轉運子之表現量，並可改善類憂鬱症狀。

Metabolic disorders and depression are two important global health issues. A high comorbidity of these two disorders suggests that an interaction exists between these two diseases. In order to comprehensively care the patients suffering from both of these disorders, it is crucial to characterize the interplays between metabolic disorders and depression. We adopted high-fat diet to induce metabolic disorders in mice. Results showed that high-fat diet led to an over-secretion of adrenocortical hormones, especially corticosterone, in mice. The high-fat diet-induced increment of corticosterone was essential for the adipogenesis contributing to adipose expansion during the development of high-fat diet-induced obesity in mice. Moreover, high-fat diet induced depression-like behaviors but not anxiety and memory deficits in mice. The complexity of astrocytic process arbors was suppressed and the expression of glial glutamate transporters. i.e. GLAST and GLT-1, was reduced in the hippocampus of mice fed with high-fat diet. Virally knockdowning the hippocampal expression of GLAST and GLT-1 induced depression-like phenotypes in naïve mice. Riluzole, a glutamatergic transmission normalizer, restored the hippocampal levels of GLAST and GLT-1 and reversed the exhibitions of depression-like behaviors in the mice fed with high-fat diet.

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