Developments in intestinal cholesterol transport and triglyceride absorption.
OBJECTIVE
To discuss recent advances in research focused on intestinal lipid handling.


RESULTS
An important strategy in reducing atherosclerosis and risk of cardiovascular events is to increase the rate of reverse cholesterol transport, including its final step; cholesterol excretion from the body. The rate of removal is determined by a complex interplay between the factors involved in regulation of intestinal cholesterol absorption. One of these factors is a process known as transintestinal cholesterol excretion. This pathway comprises transport of cholesterol directly from the blood, through the enterocyte, into the intestinal lumen. In humans, this pathway accounts for 35% of cholesterol excretion in the feces. Mechanistic studies in mice revealed that, activation of the bile acid receptor farnesoid X receptor increases cholesterol removal via the transintestinal cholesterol excretion pathway as well as decreases plasma cholesterol and triglyceride providing an interesting target for treatment of dyslipidemia in humans. The physical chemical properties of bile acids are under control of farnesoid X receptor and determine intestinal cholesterol and triglyceride solubilization as well as absorption, providing a direct link between these two important factors in the pathogenesis of cardiovascular disease. Besides bile acids, intestinal phospholipids are important for luminal lipid solubilization. Interestingly, phospholipid remodeling through LPCAT3 was shown to be pivotal for uptake of fatty acids by enterocytes, which may provide a mechanistic handle for therapeutic intervention.


CONCLUSIONS
The importance of the intestine in control of cholesterol and triglyceride homeostasis is increasingly recognized. Recently, novel factors involved in regulation of cholesterol excretion and intestinal triglyceride and fatty acid uptake have been reported and are discussed in this short review.
aDepartment of Pediatrics bDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen cDepartment of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Yared
Y
Paalvast
Jan Freark
JF
de Boer
Albert K
AK
Groen
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D001647:Bile Acids and Salts; D014280:Triglycerides; D002784:Cholesterol