Glycine betaine rather than acting only as an osmolyte also plays a role as regulator in cellular metabolism.

For many years, glycine betaine (GB) has been widely studied as an osmolyte in plants and bacteria. In animal cells, GB is an osmolyte mainly in the kidneys, but in humans many studies have shown its role as a methyl donor in homocysteine metabolism in the liver. GB is also a protein stabilizer, and thus, it became known as an osmoprotector. In many organisms GB is synthesized from choline and can also be obtained from some foods. Over the last twenty years GB has gone from being considered simply as an osmolyte to being known as a cytoprotector involved in cell metabolism and as a chemical chaperone. The aim of this review was to gather information about the role of GB in the metabolism of ethanol, lipids, carbohydrates and proteins in animals. The information generated thus far shows that GB regulates enzymes involved in the homocysteine/methionine cycle, sucrose, glucose, fructose and glycogen metabolism, in oxidative and ER-stress caused by ethanol abuse, likewise enzymes involved in lipogenesis and fatty oxidation. Besides, there are data supporting that GB regulates the transcription factors PPARα, NF-κB, FOX1, ChREBP and SREBP1 and this lets GB play a role in protein synthesis. One of the main mechanisms by which GB regulates the enzymes is by changes in their activity either because GB increases their expression or because it regulates changes in their phosphorylation status through specific kinases. GB modulates the expression of genes by changing the degree of methylation in the promoter of target genes. The exact mechanism by which GB modifies the methylation status of the promoter is not yet clear, but methyl transferases that use SAM as methyl donor and DNA methyl transferases are good candidates for this function.