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

Abstract

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.

Authors:
 [1];  [1];  [1];  [1];  [1]; ORCiD logo [1]
  1. Chemical Biology &, Exposure Sciences, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352 United States
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1452868
Report Number(s):
PNNL-SA-126308
Journal ID: ISSN 0893-228X; 453060036
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Chemical Research in Toxicology; Journal Volume: 31; Journal Issue: 5
Country of Publication:
United States
Language:
English

Citation Formats

Sadler, Natalie C., Webb-Robertson, Bobbie-Jo M., Clauss, Therese R., Pounds, Joel G., Corley, Richard, and Wright, Aaron T.. High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities. United States: N. p., 2018. Web. doi:10.1021/acs.chemrestox.8b00008.
Sadler, Natalie C., Webb-Robertson, Bobbie-Jo M., Clauss, Therese R., Pounds, Joel G., Corley, Richard, & Wright, Aaron T.. High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities. United States. doi:10.1021/acs.chemrestox.8b00008.
Sadler, Natalie C., Webb-Robertson, Bobbie-Jo M., Clauss, Therese R., Pounds, Joel G., Corley, Richard, and Wright, Aaron T.. Fri . "High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities". United States. doi:10.1021/acs.chemrestox.8b00008.
@article{osti_1452868,
title = {High-Fat Diets Alter the Modulatory Effects of Xenobiotics on Cytochrome P450 Activities},
author = {Sadler, Natalie C. and Webb-Robertson, Bobbie-Jo M. and Clauss, Therese R. and Pounds, Joel G. and Corley, Richard and Wright, Aaron T.},
abstractNote = {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.},
doi = {10.1021/acs.chemrestox.8b00008},
journal = {Chemical Research in Toxicology},
number = 5,
volume = 31,
place = {United States},
year = {Fri Mar 30 00:00:00 EDT 2018},
month = {Fri Mar 30 00:00:00 EDT 2018}
}