LXR agonist increases the lymph HDL transport in rats by promoting reciprocally intestinal ABCA1 and apo A-I mRNA levels.

Liver and intestine are major sites of apo A-I synthesis in mammals. ABCAI is reported to be involved in the secretion of nascent HDL from cultured intestinal cells. However, whether ABCA1 participates in the secretion of nascent HDL from the intestine has not been assessed directly in vivo. This study examined the effect of a synthetic LXR-agonist "TO" on the lymphatic transport of HDL in thoracic duct-cannulated rats. The feeding of a TO-containing diet resulted in an increased transport of cholesterol and apo A-I in the lymph d > 1.063 g/ml lipoprotein fraction than did the feeding of a control diet without TO. The transport of cholesterol in whole lymph was lower, whereas the transport of apo A-I was higher, in the TO group. The abundance of mRNAs for ABCAI and apo A-I in the intestine was increased in the TO group. Furthermore, although the TO-containing diet reportedly increased the serum HDL concentration in intact mice and rats, no such effect was observed in the cannulated rats. The LXR agonist stimulated in vivo the synthesis of nascent HDL by increasing reciprocally the mRNA for ABCAI and apo A-I in the intestine, thereby contributing to an increase in the circulating HDL.