The TICE Pathway: Mechanisms and Potential Clinical Applications

Transintestinal cholesterol excretion (TICE) is a non-biliary pathway that excretes excess cholesterol from the body through feces. This article focuses on the research progress of the TICE pathway in the last few years, including the discovery process of the TICE pathway, its molecular mechanism, and potential clinical applications.

Cholesterol homeostasis is vital for cardiovascular diseases, stroke, and neurodegenerative diseases. Beyond the cholesterol excretion via hepatobiliary pathway, TICE contributes significantly to reverse cholesterol transport ex vivo and in vivo. Nuclear receptors are ligand-activated transcription factors that regulate cholesterol metabolism. The farnesoid X receptor (FXR) and liver X receptor (LXR) activated, respectively, by oxysterols and bile acids promote intestinal cholesterol secretion through ABCG5/G8. Nutrient regulators and intestinal flora also modulate cholesterol secretion through the TICE pathway. TICE allows direct elimination of plasma cholesterol, which may provide an attractive therapeutic targets. TICE pathway may provide a potential target to stimulate cholesterol elimination and reduce the risk of cardiovascular diseases.