ArticleLife sciences2011
Role of high-fat diet in regulation of gene expression of drug metabolizing enzymes and transporters.
Article in Life sciences, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 108 citations in OpenAlex.
- Nutritional Status Differentially Alters Cytochrome P450 3A4 (CYP3A4) and Uridine 5'-Diphospho-Glucuronosyltransferase (UGT) Mediated Drug Metabolism: Effect of Short-Term Fasting and High Fat Diet on Midazolam Metabolism.European journal of drug metabolism and pharmacokinetics · 2018Trial
- Metabolically Healthy Obesity Is Characterized by a Distinct Proteome Signature.International journal of molecular sciences · 2025Article
- The Effect of Maternal High-Fat or High-Carbohydrate Diet during Pregnancy and Lactation on Cytochrome P450 2D (CYP2D) in the Liver and Brain of Rat Offspring.International journal of molecular sciences · 2024Article
- B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity.Nature communications · 2024Article
- Type 1 diabetes and diet-induced obesity predispose C57BL/6J mice to PMParticle and fibre toxicology · 2023Article
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- Obesity-related genomic instability and altered xenobiotic metabolism: possible consequences for cancer risk and chemotherapy.Expert reviews in molecular medicine · 2022Review
- 3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development?Metabolites · 2022Review
- Neratinib causes non-recoverable gut injury and reduces intestinal cytochrome P450 3A enzyme in mice.Toxicology research · 2022Article
- Multidrug Resistance Like Protein 1 Activity in Malpighian Tubules Regulates Lipid Homeostasis inMembranes · 2021Article
- Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants.Biomolecules · 2020Review
- Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.Pharmacology & therapeutics · 2020Review
- Review
- Protective Role of St. John's Wort and Its Components Hyperforin and Hypericin against Diabetes through Inhibition of Inflammatory Signaling: Evidence from In Vitro and In Vivo Studies.International journal of molecular sciences · 2020Review
- Background Diet Influences TMAO Concentrations Associated with Red Meat Intake without Influencing Apparent Hepatic TMAO-Related Activity in a Porcine Model.Metabolites · 2020Article
- High fat diet significantly changed the global gene expression profile involved in hepatic drug metabolism and pharmacokinetic system in mice.Nutrition & metabolism · 2020Article
- Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice.Acta pharmaceutica Sinica. B · 2020Article
- Enzymatic analysis of glucuronidation of synthetic cannabinoid 1-naphthyl 1-(4-fluorobenzyl)-1H-indole-3-carboxylate (FDU-PB-22).Xenobiotica; the fate of foreign compounds in biological systems · 2019Article
- High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network.Molecular systems biology · 2019Article
- A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aimOur aim is to investigate the molecular mechanism of regulation of gene expression of drug metabolizing enzymes (DMEs) and transporters in diet-induced obesity. MAIN
methodsAdult male CD1 mice were fed diets containing 60% kcal fat (HFD) or 10% kcal fat (LFD) for 14 weeks. RNA levels of hepatic DMEs, transporters and their regulatory nuclear receptors (NRs) were analyzed by real-time PCR. Activation of cell-signaling components (JNK and NF-κΒ) and pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) were measured in the liver. Finally, the pharmacodynamics of drugs metabolized by DMEs was measured to determine the clinical relevance of our findings. KEY
findingsRNA levels of the hepatic phase I (Cyp3a11, Cyp2b10, Cyp2a4) and phase II (Ugt1a1, Sult1a1, Sultn) enzymes were reduced ~30-60% in HFD compared to LFD mice. RNA levels of Cyp2e1, Cyp1a2 and the drug transporters, multidrug resistance proteins, (Mrp)2, Mrp3 and multidrug resistant gene (Mdr)1b were unaltered in HFD mice. Gene expression of the NRs, PXR and CAR and nuclear protein levels of RXRα was reduced in HFD mice. Cytokines, JNK and NF-κΒ were induced in HFD mice. Thus reduction in hepatic gene expression in obesity may be modulated by cross-talk between NRs and inflammation-induced cell-signaling. Sleep time of Midazolam (Cyp3a substrate) was prolonged in HFD mice, while Zoxazolamine (Cyp1a2 and Cyp2e1 substrate)-induced sleep time was unaltered. SIGNIFICANCE: This study demonstrates that gene-specific reductions in DMEs can affect specific drugs metabolized by these enzymes, thus providing a rationale to monitor the effectiveness of drug therapy in obese individuals.
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