Abstract:
Osmolytes are naturally occurring small molecular weight organic molecules, which
are accumulated in large amounts in all life forms to maintain the stability of cellular
proteins and hence preserve their functions during adverse environmental
conditions. Trimethylamine N-oxide (TMAO) and N,N,N-trimethylglycine (betaine)
are methylamine osmolytes that have been extensively studied for their diverse roles
in humans and have demonstrated opposing relations with human health. These
osmolytes are obtained from food and synthesized endogenously using dietary
constituents like choline and carnitine. Especially, gut microbiota plays a vital role in
TMAO synthesis and contributes significantly to plasma TMAO levels. The elevated
plasma TMAO has been reported to be correlated with the pathogenesis of
numerous human diseases, including cardiovascular disease, heart failure, kidney
diseases, metabolic syndrome, etc.; Hence, TMAO has been recognized as a novel
biomarker for the detection/prediction of several human diseases. In contrast,
betaine acts as a methyl donor in one-carbon metabolism, maintains cellular
S-adenosylmethionine levels, and protects the cells from the harmful effects of
increased plasma homocysteine. Betaine also demonstrates antioxidant and antiinflammatory activities and has a promising therapeutic value in several human
diseases, including homocystinuria and fatty liver disease. The present review
examines the multifarious functions of TMAO and betaine with possible
molecular mechanisms towards a better understanding of their emerging and
diverging functions with probable implications in the prevention, diagnosis, and
treatment of human diseases.
