1 research outputs found
High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities
Cytochrome P450 monooxygenase (P450)
enzymes metabolize critical
endogenous chemicals and oxidize nearly all xenobiotics. Dysregulated
P450 activities lead to altered capacity for drug metabolism and cellular
stress. The effects of mixed exposures on P450 expression and activity
are variable and elusive. A high-fat diet (HFD) is a common exposure
that results in obesity and associated pathologies including hepatotoxicity.
Herein, we report the effects of cigarette smoke on P450 activities
of normal weight and HFD induced obese mice. Activity-based protein
profiling results indicate that HFD mice had significantly decreased
P450 activity, likely instigated by proinflammatory chemicals, and
that P450 enzymes involved in detoxification, xenobiotic metabolism,
and bile acid synthesis were effected by HFD and smoke interaction.
Smoking increased activity of all lung P450 and coexposure to diet
effected P450 2s1. We need to expand our understanding of common exposures
coupled to altered P450 metabolism to enhance the safety and efficacy
of therapeutic drug dosing