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


CONCLUSIONS
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 α-tocopherol.
Laboratory of Nutrition Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, , Higashi-ku,, Fukuoka, 812-8581, Japan.
Bungo
B
Shirouchi
Yuri
Y
Nakamura
Yumiko
Y
Furukawa
Aya
A
Shiraishi
Hiroko
H
Tomoyori
Katsumi
K
Imaizumi
Masao
M
Sato
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002404:Catheterization; D002784:Cholesterol / Q000378:metabolism*; D004951:Esterification; D000069438:Ezetimibe; D008196:Lymph / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013897:Thoracic Duct
D000924:Anticholesteremic Agents; D001384:Azetidines; D002784:Cholesterol; D000069438:Ezetimibe