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Chunk #35 — Discussion and conclusions

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High Fat Diet-Induced Hepatic 18-Carbon Fatty Acids Accumulation Up-Regulates CYP2A5/CYP2A6 via NF-E2-Related Factor 2.
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It is well-known that LA and ALA are important precursors of many long chain FAs in vivo. LA and ALA cannot be synthesized by the body or cells and must be absorbed from food. Our data showed that LA and ALA at 1 mM were the most effective activator of CYP2A6. Thus, LA and ALA were chosen as the stimulus of Nrf2 silenced and over expressed HepG2 cells in the current study to scrutinize the involvement of Nrf2 in regulating CYP2A6. As shown in Figure 5, the expression of CYP2A6 induced by LA and ALA was significantly attenuated in Nrf2 silenced cells, and was markedly enhanced in Nrf2 over expressed cells, which indicated that Nrf2 expression was very crucial for the LA and ALA induced CYP2A6 up-regulation. As the classical target gene of Nrf2, GSTA1 mRNA expression change in this experiment was similar to CYP2A6, which also indirectly proved that CYP2A6 expression was influenced by Nrf2. Is the gene of CYP2A5/2A6 located on a chromosome regulated by Nrf2? Whether Nrf2 is the sole compound regulates CYP2A6 in hepatocytes steatosis? Two