Ezetimibe inhibits lymphatic transport of esterified cholesterol but not free cholesterol in thoracic lymph duct-cannulated rats

Purpose Ezetimibe has been shown to inhibit dietary cholesterol absorption in animal models and humans, but studies on lymphatic lipid transport have not yet been performed. Rats subjected to permanent lymph duct cannulation were used to investigate the effects of ezetimibe on lipid transport. Methods Rats were fed diets with and without ezetimibe (5.0 mg/kg), and their lymph was collected after feeding to quantify lymphatic lipid levels. Total cholesterol content in the intestinal mucosa was also measured. Results Rats that consumed ezetimibe had significantly lower lymphatic total cholesterol transport with the reduction of esterified cholesterol transport. According to the calculation based on cholesterol consumption, ezetimibe reduced the total cholesterol lymphatic recovery rate by 54 %. We also determined that ezetimibe significantly reduced the total cholesterol content in the intestinal mucosa. Conclusion This is the first direct evidence that ezetimibe inhibits esterified but not free cholesterol lymphatic transport in thoracic duct-cannulated rats. The results also indicate that ezetimibe is not involved in the lymphatic transport of triacylglycerols, phospholipids, or a-tocopherol.