Ask about this productRelated genes to: Fmo3 antibody
- Gene:
- FMO3 NIH gene
- Name:
- flavin containing monooxygenase 3
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 1q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 1992-10-16
- Date modifiied:
- 2018-05-03
Related products to: Fmo3 antibody
Related articles to: Fmo3 antibody
- Human cells utilize gut microbiota-derived metabolites to control systemic metabolism. Trimethylamine N-oxide (TMAO) is traditionally considered a hepatocyte-derived metabolite from microbial trimethylamine. Here we show that pancreatic β-cells also produce TMAO as an autocrine and intracellular metabolite to maintain β-cell function. β-cells synthesize TMAO via flavin-containing monooxygenase 3 (FMO3), but this machinery deteriorates in humans and rodents under diabetic and ageing conditions. β-cell-specific deletion of FMO3 depletes intracellular TMAO, leading to senescence, inflammation, and defective glucose-stimulated insulin secretion, causing age-dependent glucose intolerance in mice. Loss of FMO3 triggers nuclear factor kappa-B (NF-κB) activation, promoting senescent and inflammatory responses. Mechanistically, TMAO binds to inhibitor of kappa B alpha (IκBα), which inhibits IκBα degradation and NF-κB nuclear translocation, thereby blocking NF-κB-mediated transcription of senescent and inflammatory programs. Replenishment of FMO3 reduces NF-κB activation and senescence in aged human islets. Our findings reveal a protective role of β-cell-derived TMAO against ageing-related β-cell dysfunction. - Source: PubMed
Publication date: 2026/07/27
Wang BaominYang YumeiHo Yuen ManLin HuigeYuan JuntaoLong KekaoCheng Kenneth King YipLi Xiaomu - Diabetes mellitus type 2 (T2DM) is now considered an immunometabolic condition with a long-term low-grade inflammatory state, insulin resistance, and host-microbiome interactions. Emerging evidence suggests that gut microbiota-derived trimethylamine (TMA), its hepatic metabolite trimethylamine N-oxide (TMAO), and IRAK4-mediated innate immune signaling may contribute to metabolic inflammation and insulin resistance. However, direct mechanistic evidence linking these components remains limited, and most available data originate from preclinical studies. Gut microbiota produces TMA based on the nutrients present in the diet, such as choline, betaine, and l-carnitine, which are then oxidized in the liver to trimethylamine N-oxide (TMAO), a metabolite linked to inflammation, metabolic maladaptation, and cardiovascular issues. IRAK4, a signaling mediator of Toll-like receptor and interleukin-1 receptor, may induce NF- kB and MAPK signaling, which may contribute to metaflammation and defective insulin signaling. This overview highlights existing evidence of the TMAIRAK4 axis in the pathogenesis and insulin resistance in T2DM. We discuss current evidence suggesting that TMA/TMAO may influence innate immune signaling and inflammatory pathways associated with insulin resistance. Special attention is given to the interference with the IRSPI3KAkt-pathway by inflammatory signaling mediated by IRAK4. We also consider new treatment approaches, such as IRAK4 inhibitors, control of microbial TMA synthesis, and FMO3-based interventions. Lastly, we underscore important translational issues, such as inconsistency in the evidence about TMAO biology, microbiome diversity, insufficient human validation, and the necessity of multi-omics-based precision methods in patient stratification and personalized treatment. - Source: PubMed
Publication date: 2026/08/13
Sarma Arnabjyoti DevaDevi MoitrayeeKumar DineshChoudhary Neeraj - Metabolic bariatric surgery, such as vertical sleeve gastrectomy (VSG), is the most effective treatment for obesity, yet the molecular mechanisms remain incompletely defined. This study aims to explore the role of hepatic flavin monooxygenase 3 (FMO3) in the metabolic improvements of VSG. - Source: PubMed
Publication date: 2026/08/05
Yan HaiCao ChongTan XiaozhuoHuang XianjueLiu YanyangChu YuxiaoHe MengchengYao QiyuanHua RongShao Yikai - High-fat/choline diets can induce the production of the enterogenous metabolite trimethylamine--oxide (TMAO). TMAO is synthesized from its precursor trimethylamine (TMA), which is generated choline cleavage catalyzed by choline trimethylamine-lyase/choline TMA-lyase-activating enzyme (CutC/D) expressed by gut microbes; subsequently, TMA is oxidized to TMAO by flavin-containing monooxygenase 3 (FMO3) in the liver. While epigallocatechin gallate (EGCG) is well recognized for its gut microbiota-remodeling capacity, how it modulates TMA/TMAO metabolism through this pathway, along with the time-dependent effectiveness of EGCG intervention, remains to be elucidated. We conducted animal experiments to evaluate the inhibitory effect of time-dependent EGCG intervention on TMA/TMAO production induced by high-fat/choline diets in mice. We further identified gut bacterial strains associated with TMA levels using metagenomics and machine learning techniques, and verified the underlying mechanisms through anaerobic culture and molecular simulations. Results demonstrated EGCG significantly reduced TMA/TMAO levels in mice by regulating the choline-CutC/D-FMO3 axis. Specifically, exhibited a positive correlation with CutC enzyme activity, while showed a negative correlation with TMA levels. Mechanistically, EGCG exerted a direct bacteriostatic effect on by disrupting its cell membrane structure and inhibiting its CutC enzyme activity. Meanwhile, EGCG significantly enriched , with the abundance of this strain peaking after long-term intervention. Although does not directly degrade TMA, it indirectly reduces TMA levels by inhibiting the growth of . Long-term continuous supplementation with EGCG yielded the optimal inhibitory effect on TMA/TMAO production. Hence, EGCG exerts its function primarily through a dual mechanism: directly inhibiting the growth and CutC enzyme activity of the TMA-producing bacterium , and indirectly antagonizing by promoting the proliferation of the beneficial bacterium . This study provides novel theoretical insights into the mechanism by which EGCG alleviates TMA/TMAO metabolic disorders induced by high-fat/choline diets gut microbiota modulation. - Source: PubMed
Publication date: 2026/08/17
Wang ZhuoGao QianyaLi ShanshanFang ZhengfengHu LiangLi RanZeng ZhenLiu YuntaoLi ChengChen Hong - Flavin-containing monooxygenase 3 (FMO3) oxidizes trimethylamine (TMA), a gut-derived metabolite of dietary substrates such as choline and betaine, into trimethylamine--oxide (TMAO), which has been linked to cardiometabolic and renal diseases. We examined whether two common genetic variants, p.Glu158Lys (E158K, rs2266782) and p.Glu308Gly (E308G, rs2266780), were associated with circulating TMA and TMAO in a sub-study of a randomized clinical trial incorporating dietary substrate loads (136 fasting samples from four visits). Each Gly308 allele was associated with approximately 18% lower plasma TMAO concentrations and accounted for approximately one-third of baseline ln(TMAO) variation, independent of rs2266782 and robust to adjustment for estimated glomerular filtrate rate. In contrast, plasma TMA concentrations did not differ by genotype. No consistent genotype effects were observed for blood pressure, although systolic blood pressure showed a genotype × treatment interaction without main genotype or treatment effects. Given the small sample size and sparse genotype representation, these findings should be interpreted as exploratory and may reflect variation in TMA oxidation efficiency. In conclusion, this initial study suggests that individuals carrying the Gly308 variant exhibit lower circulating TMAO without detectable increases in TMA, consistent with preserved short-term substrate handling under controlled conditions and motivating further investigation of the TMA-TMAO pathway in larger, genotype-balanced cohorts. - Source: PubMed
Publication date: 2026/07/13
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