Basal PPAR alpha inhibits bile acid metabolism adaptation in chronic cholestatic model induced by alpha-naphthylisothiocyanate
Hua, Huiying1; Dai, Manyun1,2,3; Luo, Yishuang1; Lin, Hante1; Xu, Gangming1; Hu, Xiaowei1; Xu, Liping1; Zhang, Haoyue1; Tang, Zhiyuan1; Chang, Liming1; Liu, Aiming1; Yang, Julin4
2019
发表期刊TOXICOLOGY LETTERS
ISSN0378-4274
卷号300页码:31-39
摘要Cholestasis is one of the most challenging diseases to be treated in current hepatology. However little is known about the adaptation difference and the underlying mechanism between acute and chronic cholestasis. In this study, wild-type and Ppar alpha-null mice were orally administered diet containing 0.05% ANIT to induce chronic cholestasis. Biochemistry, histopathology and serum metabolome analysis exhibited the similar toxic phenotype between wild-type and Ppar alpha-null mice. Bile acid metabolism was strongly adapted in Ppar alpha-null mice but not in wild-type mice. The Shp and Fxr mRNA was found to be doubled in cholestatic Ppar alpha-null mice compared with the control group. Western blot confirmed the up-regulated expression of FXR in Ppar alpha-null mice treated with ANIT. Inflammation was found to be stronger in Ppar alpha-null mice than those in wild-type mice in chronic cholestasis. These data chain indicated that bile acid metabolism and inflammation signaling were different between wild-type and Ppar alpha-null mice developing chronic cholestasis, although their toxic phenotypes could not be discriminated. So basal Ppar alpha cross-talked with FXR and inhibited bile acid metabolism adaptation in chronic cholestasis.
关键词PPAR alpha FXR pathway Alpha-naphthylisothiocyanate Chronic cholestasis
资助信息National Cancer Institute Intramural Research Program; K.C. Wong Magna Fund in Ningbo University; Ningbo Natural Science Foundation
收录类别SCI
语种英语
资助项目National Cancer Institute Intramural Research Program ; K.C. Wong Magna Fund in Ningbo University ; Ningbo Natural Science Foundation[2018A610253, 2018A610253]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/63162
专题植物化学与西部植物资源持续利用国家重点实验室
通讯作者Liu, Aiming; Yang, Julin
作者单位1.Ningbo Univ, Med Sch, Ningbo 315211, Zhejiang, Peoples R China
2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Ningbo Coll Hlth Sci, Ningbo 315100, Zhejiang, Peoples R China
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GB/T 7714
Hua, Huiying,Dai, Manyun,Luo, Yishuang,et al. Basal PPAR alpha inhibits bile acid metabolism adaptation in chronic cholestatic model induced by alpha-naphthylisothiocyanate[J]. TOXICOLOGY LETTERS,2019,300:31-39.
APA Hua, Huiying.,Dai, Manyun.,Luo, Yishuang.,Lin, Hante.,Xu, Gangming.,...&Yang, Julin.(2019).Basal PPAR alpha inhibits bile acid metabolism adaptation in chronic cholestatic model induced by alpha-naphthylisothiocyanate.TOXICOLOGY LETTERS,300,31-39.
MLA Hua, Huiying,et al."Basal PPAR alpha inhibits bile acid metabolism adaptation in chronic cholestatic model induced by alpha-naphthylisothiocyanate".TOXICOLOGY LETTERS 300(2019):31-39.
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