Fmo1-KO Mouse

Fmo1, flavin containing dimethylaniline monooxygenase 1, is involved in lipid metabolism [1]. In humans, it is mainly expressed in the fetus in the liver, while in adults, it is an extrahepatic drug-metabolizing enzyme [5,6]. Fmo1 can also act on pesticides, metabolizing them in sequential enzymatic reactions with other enzymes like cytochrome P450 [4,7].

In non-alcoholic fatty liver disease (NAFLD), Fmo1 knockdown in an in vitro model suppressed lipid accumulation, down-regulation of PPARα expression, and up-regulation of ferroptosis. Conversely, Fmo1 overexpression dysregulated lipid metabolism and downregulated PPARα levels. This shows that Fmo1 promotes NAFLD progression by suppressing PPARα and inducing ferroptosis [1]. In classical papillary thyroid cancer, high Fmo1 expression independently predicted favorable recurrence-free survival, suggesting it could serve as a biomarker [2]. In Arabidopsis, Fmo1 is involved in excess light stress-induced signal transduction and cell death signaling, playing a role in systemic acquired acclimation [3].

In conclusion, Fmo1 is crucial in lipid metabolism, drug and xenobiotic metabolism. Its role in diseases such as NAFLD and classical papillary thyroid cancer, as revealed by functional studies, provides insights into disease mechanisms. Understanding Fmo1 could potentially lead to new strategies for disease treatment and prevention in these areas.

References:

1. Zou, Lin, Shi, Qin, Li, Yingxuan, Zhu, Hongling, Ma, Junhua. . FMO1 Promotes Nonalcoholic Fatty Liver Disease Progression by Regulating PPARα Activation and Inducing Ferroptosis. In Discovery medicine, 35, 612-622. doi:10.24976/Discov.Med.202335177.60. https://pubmed.ncbi.nlm.nih.gov/37553313/

2. Luo, Jing, Zhang, Bowei, Cui, Likun, Liu, Tong, Gu, Yi. 2019. FMO1 gene expression independently predicts favorable recurrence-free survival of classical papillary thyroid cancer. In Future oncology (London, England), 15, 1303-1311. doi:10.2217/fon-2018-0885. https://pubmed.ncbi.nlm.nih.gov/30757917/

3. Czarnocka, Weronika, Fichman, Yosef, Bernacki, Maciej, Mittler, Ron, Karpiński, Stanisław. 2020. FMO1 Is Involved in Excess Light Stress-Induced Signal Transduction and Cell Death Signaling. In Cells, 9, . doi:10.3390/cells9102163. https://pubmed.ncbi.nlm.nih.gov/32987853/

4. Cheropkina, Hanna, Catucci, Gianluca, Cesano, Federico, Gilardi, Gianfranco, Sadeghi, Sheila J. 2022. Bioelectrochemical platform with human monooxygenases: FMO1 and CYP3A4 tandem reactions with phorate. In Bioelectrochemistry (Amsterdam, Netherlands), 150, 108327. doi:10.1016/j.bioelechem.2022.108327. https://pubmed.ncbi.nlm.nih.gov/36446195/

5. Koukouritaki, Sevasti B, Simpson, Pippa, Yeung, Catherine K, Rettie, Allan E, Hines, Ronald N. . Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression. In Pediatric research, 51, 236-43. doi:. https://pubmed.ncbi.nlm.nih.gov/11809920/

6. Yeung, C K, Lang, D H, Thummel, K E, Rettie, A E. . Immunoquantitation of FMO1 in human liver, kidney, and intestine. In Drug metabolism and disposition: the biological fate of chemicals, 28, 1107-11. doi:. https://pubmed.ncbi.nlm.nih.gov/10950857/

7. Hodgson, E, Rose, R L, Ryu, D Y, Blake, B L, Levi, P E. . Pesticide-metabolizing enzymes. In Toxicology letters, 82-83, 73-81. doi:. https://pubmed.ncbi.nlm.nih.gov/8597134/