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Impacts on Hepatic Ontogenic Expression of Drug‐metabolizing Enzymes by High‐fat Diet‐induced Obesity in Mice
Author(s) -
Wang Pei,
Shao Xueyan,
Bao Yifan,
Chen Liming,
Zhang Lirong,
Zhong Xiaobo
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.508.3
Subject(s) - pregnane x receptor , medicine , endocrinology , offspring , cyp1a2 , constitutive androstane receptor , biology , obesity , receptor , drug metabolism , overweight , cytochrome p450 , nuclear receptor , transcription factor , metabolism , biochemistry , pregnancy , gene , genetics
The prevalence of obesity‐associated conditions increases up to 30% of general populations globally. A few studies have shown that obesity may lead to altered drug metabolism. Although changed expression of drug‐metabolizing enzymes (DMEs) is reported, the impacts on DMEs due to different obese levels (overweight, obese, and morbidly obese) have not been elucidated. Especially, limited information is available on how obesity alters the expression of DMEs in younger ages. The aim of this study is to investigate impacts of high‐fat diet‐induced obesity (DIO) on the hepatic expression of DMEs in adult and the ontogenic expression in offspring with a focus on cytochrome P450s (CYPs) in a mouse model. The expression of CYPs, as well as constitutive androstane receptor (CAR), pregnane X‐receptor (PXR), hepatocyte nuclear factor (HNF4α), and peroxisome proliferator‐activated receptor α (PPARα) was examined. Adult mice consumed 60 kcal% fat diet (HFD) for 8 or 18 weeks showed a more rapid increase of body weight than 10 kcal% fat diet (LFD) control group. The body weight gain of males was >1.5 fold greater than females in HFD groups. Consistent with the weight gain, fat accumulation was found in the livers of HFD groups. Elevated expression of most selected DMEs and transcription factors was observed in HFD groups, expect for CYP3A16 in 8‐week HFD groups, and CYP1A2 and HNF4α in 18‐week HFD groups. Day 60 offspring derived from HFD‐fed adults showed heavier body weights compared with offspring from LFD‐fed adults. Altered ontogenic expression of CYP1A1, 1A2, 2E1, and UGT1A1 was also observed in HFD offspring. Notably, the changed ontogenic patterns were accompanied by the increased expression of DMEs after day 20 in HFD offspring related to LFD groups. Moreover, similar effects on CAR, PXR, HNF4α, and PPARα were found in HFD offspring, indicating that altered expression pattern of DMEs may due to changed expression of transcription factors. Taken together, our study suggested that obese level of DIO influenced the expression of DMEs in adults and offspring and transcription factors might play roles in the altered expression of DMEs. Support or Funding Information This work was supported by grant of NIH R01GM118367 and China Scholarship Council (201707040007). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .