Postprandial chylomicron formation and fat absorption in multidrug resistance gene 2 P-glycoprotein-deficient mice

Background & Aims: It has been proposed that biliary phospholipids fulfill specific functions in the absorption of dietary fat from the intestine, but the physiological significance has not been established. The aim of this s tudy was to evaluate the role of biliary phospholipids in dietary fat absor ption in vivo by using mice homozygous or heterozygous for disruption of th e Mdr2 gene (Mdr2((-/-)), Mdr2((+/-)) and control (Mdr2((+/+))) mice. Mdr2( (-/-)), mice do not secrete phospholipids and cholesterol into bile, and bi le salt secretion is not impaired, Mdr2((+/-)), mice show only impaired (-4 0%) phospholipid secretion. Methods: Methods included an analysis of time d ependency of intestinal uptake and plasma appearance of intragastrically ad ministered (radiolabeled) triglycerides and measurement of 3-day fecal fat balance with low- and high-fat diets. Results: Intragastric administration of olive oil resulted in a rapid increase in plasma triglycerides in Mdr2(( +/+)), and Mdr2((+/-)), but not in Mdr2((-/-)), mice. The "postprandial res ponse" of plasma triglycerides could be partially restored in Mdr2((-/-)), mice by intraduodenal infusion of whole rat bile. After intragastric [H-3]t riolein administration in Triton WR1339-pretreated animals, the appearance of H-3-triglycerides in plasma was reduced by 70% in Mdr2((-/-)), compared with Mdr2((+/+)), mice, excluding accelerated lipolysis as the cause of def ective triglyceride response in Mdr2((-/-)), mice, H-3-triglycerides accumu lated in enterocytes in Mdr2((-/-)), mice. Surprisingly, the efficacy of fa t absorption as derived from balance studies was not affected and was only minimally affected in Mdr2((-/-)), mice fed low (14 energy percent)and high (35 energy percent)-fat diets, respectively tall >95%), Conclusions: The r esults show that biliary lipid secretion is necessary for postprandial appe arance in plasma of chylomicrons in vivo but not for quantitative absorptio n of dietary lipids.