Cyp4f40-KO Mouse

Cyp4f40, a member of the cytochrome P450 family 4 subfamily f, is likely involved in fatty acid metabolism and leukotriene B4 (LTB4) metabolism. In fatty acid metabolism, it may be part of pathways related to non-alcoholic fatty liver disease. In LTB4 metabolism, it could be involved in the innate mechanism to resolve tissue inflammation in skin cells [2].

In AML12 cells, knockdown of METTL3, an N6-methyladenosine methyltransferase, led to reduced Cyp4f40 expression, aggravated steatosis, and decreased levels of certain fatty acids like capric acid, gamma-linolenic acid, arachidonic acid, and docosapentaenoic acid. Cinnamaldehyde alleviated steatosis by increasing METTL3 expression, which in turn promoted Cyp4f40 expression and increased the levels of these fatty acids. This indicates that Cyp4f40-mediated fatty acid metabolism is crucial in steatosis, and METTL3 may regulate Cyp4f40 [1].

In conclusion, Cyp4f40 has essential functions in fatty acid metabolism related to non-alcoholic fatty liver disease and potentially in LTB4-mediated inflammation resolution in skin. The study of Cyp4f40 in AML12 cells with METTL3 knockdown provides insights into its role in steatosis, suggesting that it could be a potential target for treating non-alcoholic fatty liver disease [1,2].

References:

1. Xu, Ruohui, Xiao, Xiaoli, Zhang, Shengan, Ji, Guang, Dang, Yanqi. 2022. The methyltransferase METTL3-mediated fatty acid metabolism revealed the mechanism of cinnamaldehyde on alleviating steatosis. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 153, 113367. doi:10.1016/j.biopha.2022.113367. https://pubmed.ncbi.nlm.nih.gov/35780619/

2. Du, Liping, Yin, Huiyong, Morrow, Jason D, Strobel, Henry W, Keeney, Diane S. 2009. 20-Hydroxylation is the CYP-dependent and retinoid-inducible leukotriene B4 inactivation pathway in human and mouse skin cells. In Archives of biochemistry and biophysics, 484, 80-6. doi:10.1016/j.abb.2009.01.012. https://pubmed.ncbi.nlm.nih.gov/19467632/