Fmo2, flavin-containing monooxygenase 2, is involved in multiple biological processes. It has been implicated in lipid metabolism-related pathways, and is also associated with protein folding through its disulfide-bond catalytic activity [2]. Its role in various diseases has made it an important gene for functional studies. Genetic models, especially KO/CKO mouse models, have been crucial in understanding its functions.

In NAFLD, both global and hepatocyte-specific knockout of Fmo2 in mice led to increased lipogenesis, severe hepatic steatosis, inflammation, and fibrosis, while its overexpression improved NAFL/NASH. Mechanistically, Fmo2 directly interacts with SREBP1, inhibiting its translocation from the endoplasmic reticulum to the Golgi apparatus and subsequent activation, thus suppressing de novo lipogenesis [1]. In the context of myocardial infarction, genetic deletion of Fmo2 in cardiomyocytes reduced cell survival and enhanced cardiac dysfunction, while cardiomyocyte-specific overexpression conferred a protective effect. Fmo2 inhibited the activation of ER stress-induced apoptotic proteins by downregulating the unfolded protein response pathway [2]. Also, in post-myocardial infarction cardiac remodeling, CELF1 promotes this process through the suppression of Fmo2 [3].

In conclusion, Fmo2 is essential in maintaining normal lipid metabolism and protecting against ER stress-induced apoptosis in cardiomyocytes. The use of Fmo2 KO/CKO mouse models has significantly enhanced our understanding of its role in non-alcoholic fatty liver disease and ischemic heart-related conditions, providing potential therapeutic targets for these diseases.

References:

1. Ke, Changle, Xiao, Changchen, Li, Jiamin, Wu, Rongrong, Hu, Xinyang. 2023. FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1. In Hepatology (Baltimore, Md.), 81, 181-197. doi:10.1097/HEP.0000000000000643. https://pubmed.ncbi.nlm.nih.gov/37874228/

2. Liu, Qingnian, Huang, Jiniu, Ding, Hao, Hu, Xinyang, Wang, Jian'an. 2024. Flavin-containing monooxygenase 2 confers cardioprotection in ischemia models through its disulfide bond catalytic activity. In The Journal of clinical investigation, 134, . doi:10.1172/JCI177077. https://pubmed.ncbi.nlm.nih.gov/39480513/

3. Lai, Jun, Li, Likang, Liu, Jun, Jin, Wen, Ye, Zebing. 2025. CELF1 Promotes Post-myocardial Infarction Cardiac Remodeling Via Suppression of FMO2. In Cardiovascular toxicology, 25, 441-454. doi:10.1007/s12012-024-09951-5. https://pubmed.ncbi.nlm.nih.gov/40021568/