Original articles
Pei Wang, Xueyan Shao, Yifan Bao, Junjie Zhu, Liming Chen, Lirong Zhang, Xiaochao Ma, Xiao-bo Zhong. Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice[J]. Acta Pharmaceutica Sinica B, 2020, 10(1): 171-185

Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice
Pei Wanga,b, Xueyan Shaob, Yifan Baob, Junjie Zhuc, Liming Chenb, Lirong Zhanga, Xiaochao Mac, Xiao-bo Zhongb
a Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China;
b Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA;
c Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA
Abstract:
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.
Key words:    Diet-induced obesity    Overweight    High-fat diet    Drug-metabolizing enzymes    Nuclear receptors    Ontogenic expression   
Received: 2019-06-19     Revised: 2019-08-30
DOI: 10.1016/j.apsb.2019.10.009
Funds: This work was supported by the National Institutes of Health (Grant R01GM118367 to Xiao-bo Zhong, USA). Pei Wang was supported by the China Scholarship Council (Grant 201707040007).
Corresponding author: Xiao-bo Zhong     Email:xiaobo.zhong@uconn.edu
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Pei Wang
Xueyan Shao
Yifan Bao
Junjie Zhu
Liming Chen
Lirong Zhang
Xiaochao Ma
Xiao-bo Zhong

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