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Effect of nine diets on xenobiotic transporters in livers of mice.

ABSTRACT: 1. Lifestyle diseases are often caused by inappropriate nutrition habits and attempted to be treated by polypharmacotherapy. Therefore, it is important to determine whether differences in diet affect the disposition of drugs. Xenobiotic transporters in the liver are essential in drug disposition. 2. In the current study, mice were fed one of nine diets for 3 weeks. The mRNAs of 23 known xenobiotic transporters in livers of mice were quantified by microarray analysis, and validated by branched DNA assay. The mRNAs of 15 transporters were altered by at least one diet. Diet-restriction (10) and the atherogenic diet (10) altered the expression of the most number of transporters, followed by western diet (8), high-fat diet (4), lab chow (2), high-fructose diet (2) and EFA-deficient diet (2), whereas the low n-3 FA diet had no effect on these transporters. Seven of the 11 xenobiotic transporters in the Slc family, three of four in the Abcb family, two of four in the Abcc family and all three in the Abcg family were changed significantly. 3. This first comprehensive study indicates that xenobiotic transporters are altered by diet, and suggests there are likely diet-drug interactions due to changes in the expression of drug transporters.

SUBMITTER: Guo Y

PROVIDER: S-EPMC5507013 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Effect of nine diets on xenobiotic transporters in livers of mice.

Guo Ying Y Cui Julia Yue JY Lu Hong H Klaassen Curtis D CD

Xenobiotica; the fate of foreign compounds in biological systems 20150108 7

1. Lifestyle diseases are often caused by inappropriate nutrition habits and attempted to be treated by polypharmacotherapy. Therefore, it is important to determine whether differences in diet affect the disposition of drugs. Xenobiotic transporters in the liver are essential in drug disposition. 2. In the current study, mice were fed one of nine diets for 3 weeks. The mRNAs of 23 known xenobiotic transporters in livers of mice were quantified by microarray analysis, and validated by branched DN ...[more]

PMID: 25566878

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Project description:Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug resistance-associated proteins (MRP) 1 to 9, breast cancer resistance protein, and ATP-binding cassette subfamily G members 5 and 8, are responsible for the unidirectional export of endogenous and exogenous substances. Other efflux transporters [ATPase copper-transporting beta polypeptide (ATP7B) and ATPase class I type 8B member 1 (ATP8B1) as well as organic solute transporters (OST) alpha and beta] also play major roles in the transport of some endogenous chemicals across biological membranes. This review article provides a comprehensive overview of these transporters (both rodent and human) with regard to tissue distribution, subcellular localization, and substrate preferences. Because uptake and efflux transporters are expressed in multiple cell types, the roles of transporters in a variety of tissues, including the liver, kidneys, intestine, brain, heart, placenta, mammary glands, immune cells, and testes are discussed. Attention is also placed upon a variety of regulatory factors that influence transporter expression and function, including transcriptional activation and post-translational modifications as well as subcellular trafficking. Sex differences, ontogeny, and pharmacological and toxicological regulation of transporters are also addressed. Transporters are important transmembrane proteins that mediate the cellular entry and exit of a wide range of substrates throughout the body and thereby play important roles in human physiology, pharmacology, pathology, and toxicology.

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Effect of nine diets on xenobiotic transporters in livers of mice.

Publications

Effect of nine diets on xenobiotic transporters in livers of mice.

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