AUTHOR=Wang Xing-he , Cui Xiao-xu , Sun Xiao-qi , Wang Xing-hui , Li Xiao-chong , Qi Yue , Li Wei , Han Mei-yu , Muhammad Ishfaq , Zhang Xiu-ying TITLE=High Fat Diet-Induced Hepatic 18-Carbon Fatty Acids Accumulation Up-Regulates CYP2A5/CYP2A6 via NF-E2-Related Factor 2 JOURNAL=Frontiers in Pharmacology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00233 DOI=10.3389/fphar.2017.00233 ISSN=1663-9812 ABSTRACT=
To investigate the role of hepatic 18-carbon fatty acids (FA) accumulation in regulating CYP2A5/2A6 and the significance of Nrf2 in the process during hepatocytes steatosis, Nrf2-null, and wild type mice fed with high-fat diet (HFD), and Nrf2 silenced or over expressed HepG2 cells administered with 18-carbon FA were used. HE and Oil Red O staining were used for mice hepatic pathological examination. The mRNA and protein expressions were measured with real-time PCR and Western blot. The results showed that hepatic CYP2A5 and Nrf2 expression levels were increased in HFD fed mice accompanied with hepatic 18-carbon FA accumulation. The Nrf2 expression was increased dose-dependently in cells administered with increasing concentrations of stearic acid, oleic acid, and alpha-linolenic acid. The Nrf2 expression was dose-dependently decreased in cells treated with increasing concentrations of linoleic acid, but the Nrf2 expression level was still found higher than the control cells. The CYP2A6 expression was increased dose-dependently in increasing 18-carbon FA treated cells. The HFD-induced up-regulation of hepatic CYP2A5