Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 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−/−ApoB100/100 mice were fed...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Hindawi Limited
2023-01-01
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| Series: | Journal of Nutrition and Metabolism |
| Online Access: | http://dx.doi.org/10.1155/2023/5599789 |
| _version_ | 1797850526707089408 |
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| author | Markus Koponen Jaana Rysä Anna-Kaisa Ruotsalainen Olli Kärkkäinen Risto O. Juvonen |
| author_facet | Markus Koponen Jaana Rysä Anna-Kaisa Ruotsalainen Olli Kärkkäinen Risto O. Juvonen |
| author_sort | Markus Koponen |
| collection | DOAJ |
| 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−/−ApoB100/100 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−/−ApoB100/100 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. |
| first_indexed | 2024-04-09T19:02:55Z |
| format | Article |
| id | doaj.art-b5526ae210d343b097d23b7f8c997b98 |
| institution | Directory Open Access Journal |
| issn | 2090-0732 |
| language | English |
| last_indexed | 2024-04-09T19:02:55Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Journal of Nutrition and Metabolism |
| spelling | doaj.art-b5526ae210d343b097d23b7f8c997b982023-04-08T00:00:10ZengHindawi LimitedJournal of Nutrition and Metabolism2090-07322023-01-01202310.1155/2023/5599789Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 MiceMarkus Koponen0Jaana Rysä1Anna-Kaisa Ruotsalainen2Olli Kärkkäinen3Risto O. Juvonen4School of PharmacySchool of PharmacyA. I. Virtanen Institute for Molecular SciencesSchool of PharmacySchool of PharmacyConsumption 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−/−ApoB100/100 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−/−ApoB100/100 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.http://dx.doi.org/10.1155/2023/5599789 |
| spellingShingle | Markus Koponen Jaana Rysä Anna-Kaisa Ruotsalainen Olli Kärkkäinen Risto O. Juvonen Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 Mice Journal of Nutrition and Metabolism |
| title | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 Mice |
| title_full | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 Mice |
| title_fullStr | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 Mice |
| title_full_unstemmed | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 Mice |
| title_short | Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 Mice |
| title_sort | western diet decreases hepatic drug metabolism in male ldlr apob100 100 mice |
| url | http://dx.doi.org/10.1155/2023/5599789 |
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