Evaluating the appropriate oral lipid tolerance test model for investigating plasma triglyceride elevation in mice.

Evaluating the appropriate oral lipid tolerance test model for investigating plasma triglyceride elevation in mice.
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DOI:
10.1371/journal.pone.0235875
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发表时间:
2020
期刊:
影响因子:
3.7
通讯作者:
Ochiai M
Ochiai M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ochiai M

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口服脂质耐量试验(OLTT)已被用来评估肠道脂肪代谢和全身脂肪代谢,但尚未建立OLTT的啮齿动物模型。OLTT方法的差异排除了确定结果的产生,这可能会导致对测试材料的抗高甘油三酯血症效果的一些混淆。为了标准化并为OLTT制定更合适的方法学,我们研究了小鼠品系、饮食脂肪来源、禁食时间和性别对小鼠脂质诱导的高甘油三酯血症的影响。首先,在雄性ddy小鼠中观察到的脂质诱导的高甘油三酯血症比在C57BL/6N或ICR小鼠中更强烈。其次,橄榄油和大豆油的摄入显著代表了脂质诱导的高甘油三酯血症。第三,OLTT前的空腹时间对血浆甘油三酯升高有很大影响。禁食12h,但不超过48h,可引起脂质诱导的高甘油三酯血症。第四,我们探讨了表没食子儿茶素没食子酸酯(EGCG),一种绿茶多酚,对高甘油三酯血症的抑制作用。100 mg/kg的EGCG可抑制高甘油三酯血症和肠脂酶活性。第五,在雄性小鼠观察到脂质诱导的高甘油三酯血症后,观察到了EGCG诱导的抑制作用,但在雌性小鼠中没有观察到。最后,在OLTT前一周喂食高脂饮食的小鼠可以更有效地诱导脂质诱导的高甘油三酯血症。这些结果表明,禁食12小时后,雄性ddy小鼠对大豆油的反应表现出明显的脂质诱导性高甘油三酯血症。因此,确定的实验条件可能是评估脂质诱导的高甘油三酯血症的更合适的OLTT模型。
The oral lipid tolerance test (OLTT) has been known to assess intestinal fat metabolism and whole-body lipid metabolism, but rodent models for OLTT are not yet established. Differences in OLTT methodology preclude the generation of definitive results, which may cause some confusion about the anti-hypertriglyceridemia effects of the test materials. To standardize and generate more appropriate methodology for the OLTT, we examined the effects of mice strain, dietary lipid sources, fasting period, and gender on lipid-induced hypertriglyceridemia in mice. First, lipid-induced hypertriglyceridemia was more strongly observed in male ddY mice than in C57BL/6N or ICR mice. Second, the administration of olive and soybean oils remarkably represented lipid-induced hypertriglyceridemia. Third, fasting period before the OLTT largely affected the plasma triglyceride elevation. Fasting for 12 h, but less than 48 h, provoked lipid-induced hypertriglyceridemia. Fourth, we explored the suppressive effects of epigallocatechin gallate (EGCG), a green tea polyphenol, on lipid-induced hypertriglyceridemia. The administration of 100 mg/kg of EGCG suppressed lipid-induced hypertriglyceridemia and intestinal lipase activity. Fifth, EGCG-induced suppressive effects were observed after lipid-induced hypertriglyceridemia was observed in male mice, but not in female mice. Lastly, lipid-induced hypertriglyceridemia could be more effectively induced in mice fed a high-fat diet for 1 week before the OLTT. These findings indicate that male ddY mice after 12 h fasting displayed marked lipid-induced hypertriglyceridemia in response to soybean oil. Hence, the defined experiment condition may be a more appropriate OLTT model for evaluating lipid-induced hypertriglyceridemia.
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