Compensatory phospholipid digestion is required for cholesterol absorption in pancreatic phospholipase A(2)-deficient mice.
OBJECTIVE
Numerous studies have suggested phospholipid inhibition of dietary cholesterol absorption through the gastrointestinal tract. This study addressed the importance of luminal phospholipid hydrolysis in this process.


METHODS
The effect of phospholipase inhibition on cholesterol transport from intestinal lumen to the lymphatics was evaluated in lymph fistula rats. Cholesterol and phospholipid absorption efficiency in intact animals was evaluated in control and phospholipase A(2) (PLA2) gene-targeted mice.


RESULTS
The PLA2 inhibitor FPL 67047XX retarded cholesterol absorption in a lymph fistula rat model. Under basal chow-fed dietary conditions, cholesterol absorption efficiency from a single bolus meal, and plasma lipid levels, were similar among PLA2+/+, PLA2+/-, and PLA2-/- mice. Interestingly, the nonhydrolyzable phospholipid dioleoyl ether phosphatidylcholine suppressed cholesterol absorption by 10% to 18% in mice without regard to their PLA2 genotype. When 1-palmitoyl-2-[(14)C]oleoyl-phosphatidylcholine was used as the substrate, the radiolabeled phospholipid was found to be hydrolyzed and absorbed with equal efficiency in PLA2+/+, PLA2+/-, and PLA2-/- mice.


CONCLUSIONS
These results suggested that although phospholipid digestion in the intestinal lumen is a prerequisite for efficient cholesterol absorption, additional enzyme(s) can compensate for pancreatic PLA2 in catalyzing phospholipid digestion and facilitating cholesterol absorption in PLA2 knockout mice.
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0529, USA.
B L
BL
Richmond
A C
AC
Boileau
S
S
Zheng
K W
KW
Huggins
N A
NA
Granholm
P
P
Tso
D Y
DY
Hui
D000818:Animals; D002250:Carbon Radioisotopes; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics*; D016154:Digestive System Fistula / Q000378:metabolism; D005260:Female; D007408:Intestinal Absorption / Q000502:physiology*; D008196:Lymph / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010741:Phospholipases A / Q000235:genetics* / Q000378:metabolism; D054467:Phospholipases A2; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D002791:Cholesterol, Dietary; D014280:Triglycerides; D010741:Phospholipases A; D054467:Phospholipases A2