根據以往的研究指出，高脂飲食誘導代謝失調和情緒障礙。研究還表明高脂飲食導致海馬迴中GFAP的表現增加並改變星形膠質細胞的型態。星形膠質細胞被認為是大腦中的支持細胞，然而許多研究也證實星狀膠質細胞影響大腦功能。在我們的實驗中，成功以高脂飲食誘導小鼠產生代謝失調和類憂鬱行為。同時，餵食高脂飲食的小鼠海馬迴中星狀膠質細胞表現量增加、星狀膠質細胞的纖維總長度和分支數減少。Pioglitazone（PIO）屬PPAR-γ促效劑，廣泛用於第2型糖尿病（T2DM）治療，具有強效的中樞和周邊抗神經發炎作用以及抗憂鬱作用；用正常飲食或高脂飲食餵食小鼠12週後並口服給予PIO（10或20 毫克/公斤）6週治療後，進行血糖動態平衡、西方點墨法和其他生物化學實驗，結果顯示高劑量PIO（20毫克/公斤）治療可改善高脂飲食所誘導的葡萄糖不耐受性和胰島素不耐受性、改善高脂飲食誘導的類憂鬱行為（depression-like behaviors），最後逆轉星狀膠質細胞的活化、增加纖維總長和增加分支數，此外，PIO對類焦慮行為（anxiety-like behaviors）沒有影響，並且不影響小鼠的海馬迴相關記憶。總而言之，這些研究結果證實PIO可能成為代謝失調相關憂鬱症患者的潛在治療藥物。

Previous studies showed high-fat diet (HFD) induces metabolic disorders and mood disorders. Researches also had shown that HFD increases the hippocampal GFAP expression and alters the morphology of astrocyte. Astrocyte has been considered to be supporting cells in brain, nevertheless, numerous evidences have shown the role of astrocyte in affecting brain functions. In our study, we successfully generated HFD-induced metabolic disorder and depression-like behavior in mice, simultaneously. Meanwhile, the expression of astrocyte in mouse hippocampus was increased after HFD feeding. Mice fed with HFD resulted in decreasing astrocytic total process length and number of branch points. Pioglitazone (PIO), a PPAR-γ agonist and is widely used in type 2 diabetes mellitus (T2DM) treatment, which also exhibits potent central and peripheral anti-neuroinflammatory action and anti-depressive effect. After feeding mice with Chow or HFD for 12 weeks, following by oral administration of PIO (10 or 20 mg/kg) for 6 weeks, glycemic homeostasis, immunoblotting and other biochemical tests were examined. Our results showed that high dose PIO (20 mg/kg) treatment ameliorated HFD-induced impaired insulin secretion and insulin sensitivity, improved HFD-induced depression-like behaviors, reversed astrocyte activation, increased in astrocyte total process length and increased in astrocyte branch points. In addition, PIO has no effect on anxiety-like behaviors and does not affect hippocampus-related memory in mice. Taken together, these findings suggested that PIO can be a potential therapeutic agent for patients with metabolic disorder-related depression.

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