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Western Diet Decreases Hepatic Drug Metabolism in Male LDLr(−/−)ApoB(100/100) Mice
Consumption of a Western diet is an important risk factor for several chronic diseases including nonalcoholic fatty liver disease (NAFLD), but its effect on the xenobiotic metabolizing enzyme activities in the liver has been studied incompletely. In this study, male LDLr(−/−)ApoB(100/100) mice were...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081903/ https://www.ncbi.nlm.nih.gov/pubmed/37034183 http://dx.doi.org/10.1155/2023/5599789 |
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author | Koponen, Markus Rysä, Jaana Ruotsalainen, Anna-Kaisa Kärkkäinen, Olli Juvonen, Risto O. |
author_facet | Koponen, Markus Rysä, Jaana Ruotsalainen, Anna-Kaisa Kärkkäinen, Olli Juvonen, Risto O. |
author_sort | Koponen, Markus |
collection | PubMed |
description | Consumption of a Western diet is an important risk factor for several chronic diseases including nonalcoholic fatty liver disease (NAFLD), but its effect on the xenobiotic metabolizing enzyme activities in the liver has been studied incompletely. In this study, male LDLr(−/−)ApoB(100/100) mice were fed with Western diet (WD) or a standard diet for five months to reveal the effects on drug metabolism such as cytochrome P450 (CYP) oxidation and conjugation activities in the liver. Hepatic steatosis, lobular inflammation, and early fibrosis were observed in WD fed mice, but not in chow diet control mice. When compared to the controls, the WD-fed mice had significantly decreased protein-normalized CYP probe activities of 7-ethoxyresorufinO-deethylation (52%), coumarin 7-hydroxylation (26%), 7-hydroxylation of 3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin (70%), 7-hydroxylation of 3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin (78%), 7-hydroxylation of 3-(3-methoxyphenyl)coumarin (81%), and pentoxyresorufin O-depentylation (66%). Increased activity was seen significantly in sulfonation of 3-(4-methylphenyl)-7-hydroxycoumarin (289%) and cytosol catechol O-methyltranferase (COMT, 148%) in the WD group when compared to the controls. In conclusion, the WD-induced steatosis in male LDLr(−/−)ApoB(100/100) mice was associated with decreased CYP oxidation reactions but had no clear effects on conjugation reactions of glucuronidation, sulfonation, and cytosolic catechol O-methylation. Consequently, the WD may decrease the metabolic elimination of drugs compared to healthier low-fat diets. |
format | Online Article Text |
id | pubmed-10081903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-100819032023-04-08 Western Diet Decreases Hepatic Drug Metabolism in Male LDLr(−/−)ApoB(100/100) Mice Koponen, Markus Rysä, Jaana Ruotsalainen, Anna-Kaisa Kärkkäinen, Olli Juvonen, Risto O. J Nutr Metab Research Article Consumption of a Western diet is an important risk factor for several chronic diseases including nonalcoholic fatty liver disease (NAFLD), but its effect on the xenobiotic metabolizing enzyme activities in the liver has been studied incompletely. In this study, male LDLr(−/−)ApoB(100/100) mice were fed with Western diet (WD) or a standard diet for five months to reveal the effects on drug metabolism such as cytochrome P450 (CYP) oxidation and conjugation activities in the liver. Hepatic steatosis, lobular inflammation, and early fibrosis were observed in WD fed mice, but not in chow diet control mice. When compared to the controls, the WD-fed mice had significantly decreased protein-normalized CYP probe activities of 7-ethoxyresorufinO-deethylation (52%), coumarin 7-hydroxylation (26%), 7-hydroxylation of 3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin (70%), 7-hydroxylation of 3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin (78%), 7-hydroxylation of 3-(3-methoxyphenyl)coumarin (81%), and pentoxyresorufin O-depentylation (66%). Increased activity was seen significantly in sulfonation of 3-(4-methylphenyl)-7-hydroxycoumarin (289%) and cytosol catechol O-methyltranferase (COMT, 148%) in the WD group when compared to the controls. In conclusion, the WD-induced steatosis in male LDLr(−/−)ApoB(100/100) mice was associated with decreased CYP oxidation reactions but had no clear effects on conjugation reactions of glucuronidation, sulfonation, and cytosolic catechol O-methylation. Consequently, the WD may decrease the metabolic elimination of drugs compared to healthier low-fat diets. Hindawi 2023-03-31 /pmc/articles/PMC10081903/ /pubmed/37034183 http://dx.doi.org/10.1155/2023/5599789 Text en Copyright © 2023 Markus Koponen et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Koponen, Markus Rysä, Jaana Ruotsalainen, Anna-Kaisa Kärkkäinen, Olli Juvonen, Risto O. Western Diet Decreases Hepatic Drug Metabolism in Male LDLr(−/−)ApoB(100/100) Mice |
title | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr(−/−)ApoB(100/100) Mice |
title_full | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr(−/−)ApoB(100/100) Mice |
title_fullStr | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr(−/−)ApoB(100/100) Mice |
title_full_unstemmed | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr(−/−)ApoB(100/100) Mice |
title_short | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr(−/−)ApoB(100/100) Mice |
title_sort | western diet decreases hepatic drug metabolism in male ldlr(−/−)apob(100/100) mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081903/ https://www.ncbi.nlm.nih.gov/pubmed/37034183 http://dx.doi.org/10.1155/2023/5599789 |
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