Compensatory phospholipid digestion is required for cholesterol absorption in pancreatic phospholipase A2-deficient mice

Background & Aims: 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, (PLA(2)) gene-targeted mice. Results: The PLA(2) 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 PLA(2)(+/+), PLA(2)(+/-), and PLA(2)(-/-) mice, interestingly, the nonhydrolyzable phospholipid dioleoyl ether phosphatidylcholine suppressed cholesterol absorption by 10% to 18% in mice without regard to their PLA(2) genotype. When 1-palmitoyl-2-[C-14]oleoyl-phosphatidylcholine was used as the substrate, the radiolabeled phospholipid was found to be hydrolyzed and absorbed with equal efficiency in PLA(2)(+/+), PLA(2) (+/-)I and PLA(2)(-/-) 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 PLA(2) in catalyzing phospholipid digestion and facilitating cholesterol absorption in PLA(2) knockout mice.