Research Article

Western Diet Decreases Hepatic Drug Metabolism in Male LDLr−/−ApoB100/100 Mice

Table 1

The effect of a Western diet (WD) on the total probe drug metabolism of the mouse model of NAFLD. The liver microsome and cytosol fractions were prepared from the livers of eight months old male LDLr−/− ApoB100/100 mice that were fed either with chow (8 mice) or WD (10 mice) for five months.

Drug metabolizing activitynmol/(min  liver) mean (95% confidence limit)
Control dietWestern diet

Ethoxyresorufin 7-O-deethylation2.2 (1.8–2.6)1.0 (0.6–1.4)
Coumarin 7-hydroxylation1.0 (0.4–1.6)0.30 (0.08–0.52)
Pentoxyresorufin 7-O-depentylation0.018 (0.011–0.024)0.0083 (0.0054–0.011)
7-hydroxylation of 3-(3-methoxyphenyl)coumarin1.3 (0.9–1.7)0.71 (0.54–0.88)
7-hydroxylation of 3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin2.1 (1.4–2.8)1.2 (0.7–1.7)
7-hydroxylation of 3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin1.7 (1.3–2.1)1.0 (0.6–1.4)
7-O-demethylation of 3-(3-benzyloxo)phenyl-7-methoxycoumarin7.8 (5.9–9.8)5.4 (3.2–7.5)
Glucuronidation of 4-trifluoromethyl-7-hydroxycoumarin88 (54–121)57 (42–73)
Glucuronidation of 3-(1H-1, 2, 4-triazol-1-yl)-7-hydroxycoumarin0.67 (0.41–0.92)0.35 (0.10–0.61)
Sulfonation of 4-trifluoromethyl-7-hydroxycoumarin11 (7.5–14)5.9 (4.0–7.8)
Sulfonation of 3-(4-methylphenyl)-7-hydroxycoumarin8.4 (2.4–14)8.8 (5.5–12)
Cytosolic COMT3.9 (3.3–4.4)3.3 (2.7–4.0)
Microsomal COMT0.64 (0.47–0.82)0.38 (0.27–0.49)

values: ; ; Western diet vs. chow diet.