β-cells Produce Trimethylamine N-oxide (TMAO) via FMO3 to Maintain Glucose Homeostasis
Human cells utilize gut microbiota-derived metabolites to control systemic metabolism. TMAO is traditionally considered a hepatocyte-derived metabolite from microbial trimethylamine.
β-cells, like other human cells, employ the gut microbiota-liver axis to regulate systemic metabolism. The authors of this study have identified a novel β-cell-specific pathway for producing trimethylamine N-oxide (TMAO) via flavin-containing monooxygenase 3 (FMO3). This autocrine and intracellular metabolite plays a crucial role in maintaining β-cell function, particularly under conditions of ageing and diabetes. The authors' findings suggest that the FMO3-TMAO axis locally suppresses NF-κB-mediated senescence and inflammation, thereby preserving glucose homeostasis. In contrast, depletion of FMO3 in β-cells leads to senescence, inflammation, and defective glucose-stimulated insulin secretion, causing age-dependent glucose intolerance in mice. The authors' research highlights the importance of this β-cell-specific pathway in maintaining metabolic health.