Fish oil affects the metabolic process of trimethylamine N-oxide precursor through trimethylamine production and flavin-containing monooxygenase activity in male C57BL/6 mice

Abstract

High trimethylamine N-oxide (TMAO) circulation levels in vivo are closely related to atherosclerosis, chronic heart failure and chronic kidney disease. Fish oil as a commercial functional food has various positive effects on human health. The aim of the present study was to investigate the effects of long-term supplementation with fish oil on the metabolic process of TMAO after administrating a high dose of TMAO precursors. Male C57BL/6 mice were fed a diet containing 1.5% fish oil for 8 weeks. Plasma choline, trimethylamine (TMA), and TMAO pharmacokinetics were measured after treatment with choline chloride through oral gavage or trimethylammonium chloride by intraperitoneal injection. The mRNA expressions and activities of hepatic flavin-containing monooxygenases (FMOs) were also determined. Results showed that fish oil increased choline circulation levels in plasma, while suppressing the production of TMA and raising the concentration–time curve (AUC) of TMAO according to pharmacokinetic parameters. Further analysis indicated that up-regulated FMO gene expression levels and activities accelerated the metabolic process of TMAO when administrating plenty of TMAO precursors. The above results demonstrated that long-term supplementation with DHA-enriched fish oil could regulate the metabolic process of TMAO in vivo, which provides references for the development of nutritional supplements.