Trimethylamine N-oxide ameliorates hepatic damage including reduction of hepatic bile acids and cholesterol in -null mice.

There are conflicting animal experiments on the effect of trimethylamine N-oxide (TMAO), the dietary metabolite, on non-alcoholic fatty liver disease (NAFLD). This study aims to determine the effect of TMAO on NAFLD. A diet containing 0.3% TMAO was fed to farnesoid X receptor ()-null mice, a model of NAFLD, for 13 weeks. -null mice fed TMAO showed significant reductions in liver damage markers but not wild-type mice. Hepatic bile acid and cholesterol levels were significantly decreased, and triacylglycerol levels tended to decrease in TMAO-fed -null mice. Changes in mRNA levels of hepatic bile acid and cholesterol transporters and synthetic enzymes were observed, which could explain the decreased hepatic bile acid and cholesterol levels in -null mice given the TMAO diet but not in the wild-type mice. These results suggest that TMAO intake ameliorates liver damage in -null mice, further altering bile acid/cholesterol metabolism in an FXR-independent manner.