Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice.,Acta Pharmaceutica Sinica B

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Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice.
Acta Pharmaceutica Sinica B ( IF 14.7 ) Pub Date : 2019-11-28 , DOI: 10.1016/j.apsb.2019.10.009
Pei Wang _{1,

2} , Xueyan Shao ₂ , Yifan Bao ₂ , Junjie Zhu ₃ , Liming Chen ₂ , Lirong Zhang ₁ , Xiaochao Ma ₃ , Xiao-Bo Zhong ₂

Affiliation

The prevalence of obesity-associated conditions raises new challenges in clinical medication. Although altered expression of drug-metabolizing enzymes (DMEs) has been shown in obesity, the impacts of obese levels (overweight, obesity, and severe obesity) on the expression of DMEs have not been elucidated. Especially, limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children. Here, a high-fat diet (HFD) and three feeding durations were used to mimic different obese levels in C57BL/6 mice. The hepatic expression of five nuclear receptors (NRs) and nine DMEs was examined. In general, a trend of induced expression of NRs and DMEs (except for Cyp2c29 and 3a11) was observed in HFD groups compared to low-fat diet (LFD) groups. Differential effects of HFD on the hepatic expression of DMEs were found in adult mice at different obese levels. Family-based dietary style of an HFD altered the ontogenic expression of DMEs in the offspring older than 15 days. Furthermore, obese levels of parental mice affected the hepatic expression of DMEs in offspring. Overall, the results indicate that obese levels affected expression of the DMEs in adult individuals and that of their children. Drug dosage might need to be optimized based on the obese levels.

中文翻译：

肥胖水平对成年和子代小鼠核受体和药物代谢酶的肝脏表达的影响。

肥胖相关疾病的流行给临床用药带来了新的挑战。尽管肥胖中药物代谢酶 (DME) 的表达发生改变，但肥胖水平（超重、肥胖和严重肥胖）对 DME 表达的影响尚未阐明。特别是，关于父母肥胖水平是否影响儿童 DME 的个体发育表达的信息有限。在这里，使用高脂肪饮食 (HFD) 和三个喂养时间来模拟 C57BL/6 小鼠的不同肥胖水平。检查了五种核受体 (NR) 和九种 DME 的肝脏表达。一般来说，与低脂饮食（LFD）组相比，HFD 组观察到 NR 和 DME（Cyp2c29 和 3a11 除外）诱导表达的趋势。在不同肥胖水平的成年小鼠中发现 HFD 对 DME 肝脏表达的不同影响。基于家庭的 HFD 饮食风格改变了 15 天以上的后代 DME 的个体发育表达。此外，亲代小鼠的肥胖水平影响后代中 DME 的肝脏表达。总体而言，结果表明肥胖水平影响成人及其子女的 DME 表达。药物剂量可能需要根据肥胖水平进行优化。

更新日期：2019-11-29

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