High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities

Journal Article · Fri Mar 30 04:00:00 EDT 2018 · Chemical Research in Toxicology

DOI:https://doi.org/10.1021/acs.chemrestox.8b00008· OSTI ID:1452868

Sadler, Natalie C. ^[1]; Webb-Robertson, Bobbie-Jo M. ^[1]; Clauss, Therese R. ^[1]; Pounds, Joel G. ^[1]; Corley, Richard ^[1]; Wright, Aaron T. ^[1]

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1. Chemical Biology &, Exposure Sciences, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352 United States

Cytochrome P450 monooxygenases (P450) are key to the metabolism of myriad endogenous chemicals and xenobiotics, including the majority of therapeutic drugs. Dysregulated P450 activities can lead to altered drug metabolism and toxicity, oxidative stress, and inflammation; all physiological states frequently charged as the impetus for various chronic pathologies. We characterized the impact of common xenobiotic exposures, specifically high-fat diet and active or passive cigarette smoke, on the functional capacity of hepatic and pulmonary P450s. We employed an activity-based protein profiling approach to characterize the identity and activity level of measured individual P450 isoforms. Our results confirm expectations of significant alterations in pulmonary P450s due to cigarette smoke, but now reveal the repressive impact of high-fat diet-induced obesity on many hepatic P450s activities, and the dynamic alterations due to concomitant diet and smoke exposures on liver and lung P450 activities impacting drug metabolism and pathways of inflammation.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1452868
• Report Number(s): PNNL-SA-126308; 453060036
• Journal Information: Chemical Research in Toxicology, Journal Name: Chemical Research in Toxicology Journal Issue: 5 Vol. 31; ISSN 0893-228X
• Publisher: American Chemical Society (ACS)
• Country of Publication: United States
• Language: English