Induction of cytochrome P450IIE1 in the obese overfed rat.

摘要: Cytochrome P450IIE1 (IIE1) is a microsomal xenobiotic-activating enzyme that inducible not only by various chemical agents but also fasting and diabetes. Using rat model mimics human obesity, we have found hepatic IIE1 levels are increased this common clinical disorder. Liver microsomes from rats made obese feeding with an energy-dense diet displayed elevated aggregate P450 content (+28%) enhanced catalytic activities associated IIE1, including low-Km N-nitrosodimethylamine demethylation (+66%), aniline hydroxylation (+52%), p-nitrophenol (+170%), acetaminophen-cysteine conjugate formation (+28%). In contrast, obesity had no significant effect on cytochrome b5 content, reductase activity, benzphetamine demethylation, or erythromycin the latter two reactions being linked IIC11 IIIA1, respectively. The enhancement of IIE1-dependent drug-metabolizing noted in liver was paralleled similar increase (111%) protein these animals, as assessed immunoblots developed anti-hamster IgG. Anti-IIE1-inhibitable rates metabolism, reaction highly correlated (r = 0.88, p less than 0.01), were over 3-fold higher nonobese controls, providing additional evidence for obesity-related IIE1. induction pathophysiological condition may provide biochemical basis incidence occult disease certain cancers individuals.