Trimethylamine N‐Oxide Aggravates Liver Steatosis through Modulation of Bile Acid Metabolism and Inhibition of Farnesoid X Receptor Signaling in Nonalcoholic Fatty Liver Disease

May 17, 2019Molecular nutrition & food research

Trimethylamine N-Oxide worsens fatty liver by changing bile acid processing and blocking a key liver receptor in nonalcoholic fatty liver disease

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Abstract

Serum levels of trimethylamine N-oxide (TMAO) are positively correlated with total bile acid levels in nonalcoholic fatty liver disease (NAFLD) patients.

  • NAFLD patients exhibit markedly higher serum levels of total bile acids compared to controls.
  • TMAO may impair liver function and increase triglyceride accumulation in a mouse model on a high-fat diet.
  • Increased TMAO is associated with elevated hepatic expression of cholesterol 7 alpha hydroxylase (CYP7A1).
  • TMAO shifts bile acid composition toward species that antagonize farnesoid X receptor (FXR) activity.
  • Blocking CYP7A1 or activating FXR may prevent TMAO-induced lipogenesis in liver cells.

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