NDLI: High fat diet significantly changed the global gene expression profile involved in hepatic drug metabolism and pharmacokinetic system in mice

Content Provider	Springer Nature : BioMed Central
Author	He, Yuqi Yang, Tao Du, Yimei Qin, Lin Ma, Feifei Wu, Zunping Ling, Hua Yang, Li Wang, Zhengtao Zhou, Qingdi Ge, Guangbo Lu, Yanliu
Abstract	Background High fat diet impact transcription of hepatic genes responsible for drug metabolism and pharmacokinetics. Until now, researches just focused on a couple specific genes without a global profile showing. Age-dependent manner was also not noted well. This study aims to investigate the high fat diet effect on transcriptome of drug metabolism and pharmacokinetic system in mouse livers and show the age-dependent evidence. Methods C57BL/6 male mice were used in this experiment. High fat diet was used to treat mice for 16 and 38 weeks. Serum total cholesterol, low density lipoprotein cholesterol, aspartate transaminase, and alanine transaminaselevels were measured. Meanwhile, Histology, RNA-Seq, RT-PCR analysis and fourteen major hepatic bile acids quantification were performed for the liver tissues. Data was mined at levels of genes, drug metabolism and pharmacokinetic sysem, and genome wide. Results Treatment with high fat diet for 38 weeks significantly increased levels of serum lipids as well as aspartate transaminase, and alanine transaminase. Meanwhile, lipid accumulation in livers was observed. At week 38 of the experiment, the profile of 612 genes involved in drug metabolism and pharmacokinetics was significantly changed, indicated by a heatmap visulization and a principal component analysis. In total 210 genes were significantly regulated. Cyp3a11, Cyp4a10, and Cyp4a14 were down-regulated by 10–35 folds, while these three genes also were highly expressed in the liver. High fat diet regulated 11% of genome-wide gene while 30% of genes involved in the hepatic drug metabolism and pharmacokinetic system. Genes, including Adh4, Aldh1b1, Cyp3a11, Cyp4a10, Cyp8b1, Fmo2, Gsta3, Nat8f1, Slc22a7, Slco1a4, Sult5a1, and Ugt1a9, were regulated by high fat diet as an aging-dependent manner. Bile acids homeostasis, in which many genes related to metabolism and transportation were enriched, was also changed by high fat diet with an aging-dependet manner. Expression of genes in drug metabolism and disposition system significantly correlated to serum lipid profiles, and frequently correlated with each other. Conclusions High fat diet changed the global transcription profile of hepatic drug metabolism and pharmacokinetic system with a age-dependent manner.
Related Links	https://nutritionandmetabolism.biomedcentral.com/counter/pdf/10.1186/s12986-020-00456-w.pdf
Ending Page	15
Page Count	15
Starting Page	1
File Format	HTM / HTML
ISSN	17437075
DOI	10.1186/s12986-020-00456-w
Journal	Nutrition & Metabolism
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2020-05-24
Access Restriction	Open
Subject Keyword	Clinical Nutrition Metabolic Diseases High fat diet Drug metabolism and pharmacokinetic RNA-Seq Transcriptome
Content Type	Text
Resource Type	Article
Subject	Medicine Endocrinology, Diabetes and Metabolism Nutrition and Dietetics
Journal Impact Factor	3.9/2023
5-Year Journal Impact Factor	4.3/2023

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