Trimethylamine oxide (TMAO) is a common and compatible osmolyte in muscle tissues of marine organisms that is often credited with counteracting protein-destabilizing forces. However, the origin and synthetic pathways of TMAO are actively debated. Here, we examine the distribution of TMAO in marine animals and report a correlation between TMAO and acylglycerol storage. We put forward the hypothesis that TMAO is derived, at least in part, from the hydrolysis of phosphatidylcholine, endogenous or dietary, for storage as diacylglycerol ethers and triacylglycerols. TMAO is synthesized from the trimethylammonium moiety of choline, thus released, and is retained as a compatible solute in concentrations reflecting the amount of lipid stored in the body. A variation on this theme is proposed for sharks.