Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis

Mohamed A. Abdelmegeed, Youngshim Choi, Grzegorz Godlewski, Seung Kwon Ha, Atrayee Banerjee, Sehwan Jang, Byoung Joon Song

Research output: Contribution to journalArticle

Abstract

Cytochrome P450-2E1 (CYP2E1) increases oxidative stress. High hepatic cholesterol causes non-alcoholic steatohepatitis (NASH) and fibrosis. Thus, we aimed to study the role of CYP2E1 in promoting liver fibrosis by high cholesterol-containing fast-food (FF). Male wild-type (WT) and Cyp2e1-null mice were fed standard chow or FF for 2, 12, and 24 weeks. Various parameters of liver fibrosis and potential mechanisms such as oxidative and endoplasmic reticulum (ER) stress, inflammation, and insulin resistance (IR) were studied. Indirect calorimetry was also used to determine metabolic parameters. Liver histology showed that only WT fed FF (WT-FF) developed NASH and fibrosis. Hepatic levels of fibrosis protein markers were significantly increased in WT-FF. The nitroxidative stress marker iNOS, but not CYP2E1, was significantly elevated only in FF-fed WT. Serum endotoxin, TLR-4 levels, and inflammatory markers were highest in WT-FF. FAS, PPAR-α, PPAR-γ, and CB1-R were markedly altered in WT-FF. Electron microscopy and immunoblot analyses showed significantly higher levels of ER stress in FF-fed WT. Indirect calorimetry showed that Cyp2e1-null-mice fed FF exhibited consistently higher total energy expenditure (TEE) than their corresponding WT. These results demonstrate that CYP2E1 is important in fast food-mediated liver fibrosis by promoting nitroxidative and ER stress, endotoxemia, inflammation, IR, and low TEE.

Original languageEnglish (US)
Article number39764
JournalScientific Reports
Volume7
DOIs
StatePublished - Jan 4 2017
Externally publishedYes

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Fast Foods
Cytochrome P-450 CYP2E1
Fibrosis
Liver
Endoplasmic Reticulum Stress
Liver Cirrhosis
Indirect Calorimetry
Peroxisome Proliferator-Activated Receptors
Fatty Liver
Energy Metabolism
Insulin Resistance
Cholesterol
Inflammation
Endotoxemia
Endotoxins
Histology
Electron Microscopy
Oxidative Stress

ASJC Scopus subject areas

  • General

Cite this

Abdelmegeed, M. A., Choi, Y., Godlewski, G., Ha, S. K., Banerjee, A., Jang, S., & Song, B. J. (2017). Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis. Scientific Reports, 7, [39764]. https://doi.org/10.1038/srep39764

Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis. / Abdelmegeed, Mohamed A.; Choi, Youngshim; Godlewski, Grzegorz; Ha, Seung Kwon; Banerjee, Atrayee; Jang, Sehwan; Song, Byoung Joon.

In: Scientific Reports, Vol. 7, 39764, 04.01.2017.

Research output: Contribution to journalArticle

Abdelmegeed, MA, Choi, Y, Godlewski, G, Ha, SK, Banerjee, A, Jang, S & Song, BJ 2017, 'Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis', Scientific Reports, vol. 7, 39764. https://doi.org/10.1038/srep39764
Abdelmegeed MA, Choi Y, Godlewski G, Ha SK, Banerjee A, Jang S et al. Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis. Scientific Reports. 2017 Jan 4;7. 39764. https://doi.org/10.1038/srep39764
Abdelmegeed, Mohamed A. ; Choi, Youngshim ; Godlewski, Grzegorz ; Ha, Seung Kwon ; Banerjee, Atrayee ; Jang, Sehwan ; Song, Byoung Joon. / Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis. In: Scientific Reports. 2017 ; Vol. 7.
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