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 activity
nmol/(min liver) mean (95% confidence limit)
Control diet
Western diet
Ethoxyresorufin 7-O-deethylation
2.2 (1.8–2.6)
1.0 (0.6–1.4)
Coumarin 7-hydroxylation
1.0 (0.4–1.6)
0.30 (0.08–0.52)
Pentoxyresorufin 7-O-depentylation
0.018 (0.011–0.024)
0.0083 (0.0054–0.011)
7-hydroxylation of 3-(3-methoxyphenyl)coumarin
1.3 (0.9–1.7)
0.71 (0.54–0.88)
7-hydroxylation of 3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin
2.1 (1.4–2.8)
1.2 (0.7–1.7)
7-hydroxylation of 3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin
1.7 (1.3–2.1)
1.0 (0.6–1.4)
7-O-demethylation of 3-(3-benzyloxo)phenyl-7-methoxycoumarin
7.8 (5.9–9.8)
5.4 (3.2–7.5)
Glucuronidation of 4-trifluoromethyl-7-hydroxycoumarin
88 (54–121)
57 (42–73)
Glucuronidation of 3-(1H-1, 2, 4-triazol-1-yl)-7-hydroxycoumarin
0.67 (0.41–0.92)
0.35 (0.10–0.61)
Sulfonation of 4-trifluoromethyl-7-hydroxycoumarin
11 (7.5–14)
5.9 (4.0–7.8)
Sulfonation of 3-(4-methylphenyl)-7-hydroxycoumarin