Department of Animal Science, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan.
PLoS One. 2020 Oct 6;15(10):e0235875. doi: 10.1371/journal.pone.0235875. eCollection 2020.
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.
口服脂质耐量试验（OLTT）已被用于评估肠道脂肪代谢和全身脂质代谢，但尚未建立用于 OLTT 的啮齿动物模型。由于 OLTT 方法学的差异，无法得出明确的结果，这可能导致人们对试验材料的抗高甘油三酯血症作用产生一些混淆。为了使 OLTT 标准化并产生更合适的方法，我们研究了小鼠品系、饮食脂质来源、禁食期和性别对小鼠脂质诱导的高甘油三酯血症的影响。首先，雄性 ddY 小鼠比 C57BL/6N 或 ICR 小鼠更容易观察到脂质诱导的高甘油三酯血症。其次，橄榄油和大豆油的给药显著代表了脂质诱导的高甘油三酯血症。第三，OLTT 前的禁食期对血浆甘油三酯升高有很大影响。禁食 12 小时，但不到 48 小时，会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，对脂质诱导的高甘油三酯血症的抑制作用。给予 100mg/kg 的 EGCG 可抑制脂质诱导的高甘油三酯血症和肠脂肪酶活性。第五，在雄性小鼠中观察到脂质诱导的高甘油三酯血症后，观察到 EGCG 诱导的抑制作用，但在雌性小鼠中未观察到。最后，在 OLTT 前 1 周给予高脂肪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。这些发现表明，禁食 12 小时后的雄性 ddY 小鼠对大豆油表现出明显的脂质诱导的高甘油三酯血症。因此，定义明确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。
