Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice
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 eluci...
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doaj-2d6d8b3eb3324aabb84355023ee4aadd2020-11-25T02:19:35ZengElsevierActa Pharmaceutica Sinica B2211-38352020-01-01101171185Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring micePei Wang0Xueyan Shao1Yifan Bao2Junjie Zhu3Liming Chen4Lirong Zhang5Xiaochao Ma6Xiao-bo Zhong7Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China; Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USADepartment of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA; Corresponding author. Tel.: +1 860 486 3697; fax: +1 860 486 5792.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 expressionhttp://www.sciencedirect.com/science/article/pii/S2211383519308585 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pei Wang Xueyan Shao Yifan Bao Junjie Zhu Liming Chen Lirong Zhang Xiaochao Ma Xiao-bo Zhong |
spellingShingle |
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 Acta Pharmaceutica Sinica B |
author_facet |
Pei Wang Xueyan Shao Yifan Bao Junjie Zhu Liming Chen Lirong Zhang Xiaochao Ma Xiao-bo Zhong |
author_sort |
Pei Wang |
title |
Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice |
title_short |
Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice |
title_full |
Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice |
title_fullStr |
Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice |
title_full_unstemmed |
Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice |
title_sort |
impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice |
publisher |
Elsevier |
series |
Acta Pharmaceutica Sinica B |
issn |
2211-3835 |
publishDate |
2020-01-01 |
description |
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 |
url |
http://www.sciencedirect.com/science/article/pii/S2211383519308585 |
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