Trimethylamine N-oxide (TMAO) is a colorless amine oxide produced from choline, betaine, and carnitine via intestinal microbial metabolism that accumulates in tissues of marine animals and prevents the protein-damaging effects of urea.Trimethylamine N-oxide induces inflammation through activation of ROS/NLRP3 inflammasomes, which can induce fibroblast differentiation and cardiac fibrosis.

In vitro, the treatment of fibroblasts with Trimethylamine N-oxide (TMAO) results in an increase in both the size and migration of fibroblasts compared to untreated fibroblasts. TMAO induces an elevation in TGF-β receptor I expression, leading to the phosphorylation of Smad2 and an up-regulation in the expression of α-SMA and collagen I. Concurrently, the ubiquitination of TGF-βRI is decreased in neonatal mouse fibroblasts following Trimethylamine N-oxide treatment. Additionally, Trimethylamine N-oxide inhibits the expression of smurf2 [3].
Trimethylamine N-oxide is commonly found in the tissues of various marine organisms, where it serves as a protective factor against the adverse effects of temperature, salinity, high urea, and hydrostatic pressure [2].

Trimethylamine N-oxide can be utilized in animal modeling to establish a model of cardiac fibrosis.