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题名: 抗精神病藥物對Adiponectin基因表現及分泌調控機制影響之探討
The Effect of Antipsychotics on Adiponectin Gene Expression and Secretion
作者: 陳秀儀;林朝誠
贡献者: NTOU:Institute of Bioscience and Biotechnology
國立臺灣海洋大學:生物科技研究所
日期: 2008-08
上传时间: 2011-06-28T07:17:43Z
出版者: 行政院國家科學委員會
摘要: 摘要:現今臨床上常使用的第二代抗精神病藥物(又稱非典型抗精神病藥物)易造成 體重增加,使精神病患罹患糖尿病、心血管疾病及其它併發症的風險顯著提高。 目前對於抗精神病藥物引發體重增加之機制並不清楚。由於肥胖者血清中 adiponectin 濃度較瘦者來得低,且研究顯示血清中低adiponectin 易增加胰島素阻 抗性及冠狀動脈硬化的罹患率。然而adiponectin 與抗精神病藥物之相關研究非常 缺乏,為了解是否adiponectin 與抗精神病藥物引發體重增加是否具相關性,本實 驗室在臨床上針對體重過重之精神病患換成低體重增加量的抗精神病藥物一年 間,偵測病患第零、三、六及十二月血清中adiponectin 濃度,結果adiponectin 濃度增加與體重及腰圍呈現負相關,與HDL(high density lipoprotein)呈正相關, 即病患換藥後體重減輕,血清中adiponectin 增加且增加降低心血管疾病發生的 HDL 的產生。 而完全由脂肪細胞分泌的 adiponectin 可進行autocrine 及paracrine 作用於脂 肪細胞本身、腦部、肝臟…等,由於肥胖主要是因脂肪細胞數量的增多及脂肪細 胞本身體積的變大。故本計劃主要著重在脂肪細胞研究抗精神病藥物如何影響脂 肪細胞產生adiponectin,及其對脂肪細胞的影響,初步結果顯示易引發體重增加 的抗精神病藥物clozapine 可直接作用於脂肪細胞,降低adiponectin 的mRNA 及 蛋白分泌表現量。因adiponectin 基因表現及分泌調控機制相當複雜,擬從肥胖易 產生之現象來探討其對adiponectin 基因表現及分泌調控機制之影響,故未來三年 擬探討(1)抗精神病藥物是否透過影響脂肪細胞的分化而影響adiponectin 的基因 表現和分泌(2)抗精神病藥物是否影響adiponectin 基因轉錄之誘導(induction)及抑 制(repression)而調控其基因表現和分(3)抗精神病藥物是否透過影響脂肪細胞的 代謝即脂質的分解(lipolysis)及合成(adipogenesis) 而影響adiponectin 的基因表現 和分泌(4) 抗精神病藥物是否透缺氧(hypoxia)、過氧壓力(oxidative stress)、內質 網壓力(endoplasmic reticulum stress)及發炎反應(inflammation)而影響adiponectin 的基因表現和分泌。我們預期此計劃將有助於了解抗精神病藥物與對脂肪細胞的 影響,釐清抗精神病藥物與adiponectin 之關聯性,作為未來研究臨床精神用藥之 參考。
abstract:Second-generation antipsychotics (also called atypical antipsychotics) cause the side effect of weight gain in a significant portion of patients, which raises the risk of getting diabetes, cardiovascular and other co-morbid diseases. The mechanism of antipsychotics-induced weight gain is unknown. Several studies demonstrated that adiponectin levels are lower in obese than those in lean subjects. Hypoadiponectin can induce insulin resistance and increase risk for atherosclerotic diseases. However, the relationship between antipsychotics and adiponectin remains poorly characterized. In order to study the association between adiponectinand antipsychotic-induced weight gain, we recruited chronic psychotic inpatients with overweight and evaluate the change in adiponectin after switching to low weight gain antipsychotics from taking other antisychotics in overweight of chronic psychotic patients for one year. A positive correlation was found between high molecular weight adiponectin and HDL(high density lipoprotein), negative for body weight and waist circumference. These results provide switching low weight gain antipsychotics to result in weight loss can increase serum adiponectin and HDL, further lower incidence of atherosclerotic diseases. Adiponectin, an abundant serum hormone exclusively synthesized by white adipocyte tissue. It has autocrine and paracrine to action on adipocyte and peripheral tissues, for example, brain, liver…Our project focus on how antipsychotics affect adiponectin productin and its action on adipocyte. Preliminary results indicated induced weight gain antipsychotics,clozapine can decrease adiponectin mRNA and secretion. Regulation of adiponectin gene expression and secretion is very complex. To explore the effect of antipsychotics on adiponectin gene expression and secretion, we plan he following goals in the next three years below: ..Elucidate whether antipychotics affect adiponectin gene expression and secretion through adipocyte differentiation .Elucidate whether antipychotics affect adiponectin gene expression and secretion through induction and repression of adiponectin gene .Elucidate whether antipychotics affect adiponectin gene expression and secretion through adipogenesis and lipolysis. 2007/12/31 修訂 .Elucidate whether antipychotics affect adiponectin gene expression and secretion through hypoxia, oxidative stress, endoplasmic reticulum stress and inflammation. We believe these approaches outlined above may help understand the effect of antipsychotics on adipocyte and adiponectin gene expression and secretion. It may have implications for further clinical researches and practice of antipsychotic medications.
關聯: NSC97-2320-B019-001
URI: http://ntour.ntou.edu.tw/ir/handle/987654321/9853
显示于类别:[生命科學暨生物科技學系] 研究計畫

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