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

Nutrition & Metabolism - Tập 17 - Trang 1-15 - 2020
Yuqi He1,2, Tao Yang1, Yimei Du1, Lin Qin1, Feifei Ma1, Zunping Wu1, Hua Ling3, Li Yang2, Zhengtao Wang2, Qingdi Zhou4, Guangbo Ge1,5, Yanliu Lu1,2
1The Key Laboratory of the Minstry of Education of the Basic Pharmacology and the Joint International Research Laboratory of Ethnomedicine of the Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi City, China
2Institute of Chinese Materia Medica, Shanghai Key Laboratory of Complex Prescription and the Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines , Shanghai University of Traditional Chinese Medicine, Shanghai, China
3School of Pharmacy, Philadelphia College of Osteopathic Medicine, Suwanee, USA
4School of Chemistry, The University of Sydney, Camperdown, Australia
5Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China

Tóm tắt

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. 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. 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. High fat diet changed the global transcription profile of hepatic drug metabolism and pharmacokinetic system with a age-dependent manner.

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Nutrition & Metabolism

Tập 17

1-15

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