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大鼠模型中胆碱或蛋氨酸-胆碱缺乏饮食诱导的脂肪变性的基本致病和代谢差异。

Essential pathogenic and metabolic differences in steatosis induced by choline or methione-choline deficient diets in a rat model.

作者信息

Veteläinen Reeta, van Vliet Arlène, van Gulik Thomas M

机构信息

Department of Surgery (Surgical Laboratory), Academic Medical Center, Amsterdam, The Netherlands.

出版信息

J Gastroenterol Hepatol. 2007 Sep;22(9):1526-33. doi: 10.1111/j.1440-1746.2006.04701.x.

Abstract

BACKGROUND AND AIM

Choline deficient (CD) and methione-choline deficient (MCD) diets are rodent models for steatosis, with potentially dissimilar biochemical backgrounds. The aim of this study was to assess the metabolic and pathological derangements in rats fed CD and MCD diets.

METHODS

Male Wistar rats received CD or MCD diet up to 7 weeks. Nutritional status, liver histopathology, Kupffer cell-mediated inflammation and injury, oxidative stress via thiobarbituric reactive species (TBARS), hepatic and plasma glutathione (GSH) and insulin homeostasis were assessed.

RESULTS

In CD-fed rats, mainly microvesicular steatosis developed with occasional inflammatory cells. In MCD-fed rats, macrovesicular steatosis progressed to steatohepatitis (collagen deposition, activated stellate cells). Hepatic TBARS was increased and GSH decreased in the MCD-fed rats compared to no changes in the CD-fed rats. The CD-fed rats developed obesity, dyslipidemia and insulin resistance, in contrast to undetectable plasma lipids, unaffected insulin homeostasis and loss of body weight in the MCD-fed rats.

CONCLUSIONS

The CD diet induced uncomplicated steatosis as compared to progressive inflammation and fibrinogenesis in the MCD diet. CD and MCD diets represent two pathogenically different models of steatosis. Although equivalence for the outcome of both diets can be found in clinical steatosis, the results of models using these diets should be compared with caution.

摘要

背景与目的

胆碱缺乏(CD)和蛋氨酸 - 胆碱缺乏(MCD)饮食是用于脂肪变性的啮齿动物模型,其生化背景可能不同。本研究的目的是评估喂食CD和MCD饮食的大鼠的代谢和病理紊乱情况。

方法

雄性Wistar大鼠接受CD或MCD饮食长达7周。评估营养状况、肝脏组织病理学、库普弗细胞介导的炎症和损伤、通过硫代巴比妥酸反应性物质(TBARS)评估的氧化应激、肝脏和血浆谷胱甘肽(GSH)以及胰岛素稳态。

结果

在喂食CD饮食的大鼠中,主要出现微泡性脂肪变性,偶见炎性细胞。在喂食MCD饮食的大鼠中,大泡性脂肪变性进展为脂肪性肝炎(胶原沉积、星状细胞活化)。与喂食CD饮食的大鼠无变化相比,喂食MCD饮食的大鼠肝脏TBARS增加而GSH降低。喂食CD饮食的大鼠出现肥胖、血脂异常和胰岛素抵抗,而喂食MCD饮食的大鼠血浆脂质检测不到、胰岛素稳态未受影响且体重减轻。

结论

与MCD饮食中渐进性炎症和纤维蛋白生成相比,CD饮食诱导单纯性脂肪变性。CD和MCD饮食代表脂肪变性的两种致病机制不同的模型。尽管在临床脂肪变性中可发现两种饮食结果的等效性,但使用这些饮食的模型结果应谨慎比较。

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