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首页> 外文期刊>Physiological Reports >Male apoE*3?￠????Leiden.CETP mice on high?￠????fat high?￠????cholesterol diet exhibit a biphasic dyslipidemic response, mimicking the changes in plasma lipids observed through life in men
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Male apoE*3?￠????Leiden.CETP mice on high?￠????fat high?￠????cholesterol diet exhibit a biphasic dyslipidemic response, mimicking the changes in plasma lipids observed through life in men

机译：高脂高脂饮食的雄性apoE * 3？Leiden.CETP小鼠表现出双相血脂异常反应，模仿了男性一生中观察到的血脂变化

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Physiological adaptations resulting in the development of the metabolic syndrome in man occur over a time span of several decades. This combined with the prohibitive financial cost and ethical concerns to measure key metabolic parameters repeatedly in subjects for the major part of their life span makes that comprehensive longitudinal human data sets are virtually nonexistent. While experimental mice are often used, little is known whether this species is in fact an adequate model to better understand the mechanisms that drive the metabolic syndrome in man. We took up the challenge to study the response of male apoE*3?￠????Leiden.CETP mice (with a humanized lipid profile) to a high?￠????fat high?￠????cholesterol diet for 6????months. Study parameters include body weight, food intake, plasma and liver lipids, hepatic transcriptome, VLDL ?￠???? triglyceride production and importantly the use of stable isotopes to measure hepatic de novo lipogenesis, gluconeogenesis, and biliary/fecal sterol secretion to assess metabolic fluxes. The key observations include (1) high inter?￠????individual variation; (2) a largely unaffected hepatic transcriptome at 2, 3, and 6????months; (3) a biphasic response curve of the main metabolic features over time; and (4) maximum insulin resistance preceding dyslipidemia. The biphasic response in plasma triglyceride and total cholesterol appears to mimic that of men in cross?￠????sectional studies. Combined, these observations suggest that studies such as these can help to delineate the causes of metabolic derangements in patients suffering from metabolic syndrome.
机译：导致人类代谢综合征发展的生理适应发生在数十年的时间跨度内。再加上无法承受的财务成本和道德考量，无法在受试者的生命周期的大部分时间内重复测量关键代谢参数，这使得实际上不存在完整的纵向人类数据集。尽管经常使用实验小鼠，但对于这种物种实际上是否是一个能更好地理解人类代谢综合症机制的适当模型，鲜为人知。我们接受了一项挑战，以研究雄性apoE * 3？Leiden.CETP小鼠（具有人源化脂质特征）对高脂肪高胆固醇饮食的反应持续6个月？研究参数包括体重，食物摄入量，血浆和肝脂质，肝转录组，VLDL。甘油三酸酯的产生，重要的是使用稳定的同位素来测量肝脏的新生脂肪形成，糖异生和胆/粪便甾醇分泌，以评估代谢通量。主要观察结果包括：（1）个体间高变异性; （2）在第2、3和6个月大不受影响的肝转录组; （3）主要代谢特征随时间的双相反应曲线; （4）血脂异常之前的最大胰岛素抵抗。在横断面研究中，血浆甘油三酸酯和总胆固醇的双相反应似乎与男性相似。综合起来，这些观察结果表明，诸如此类的研究可以帮助描述患有代谢综合征的患者的代谢紊乱的原因。

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