Postprandial chylomicron formation and fat absorption in multidrug resistance gene 2 P-glycoprotein-deficient mice.
OBJECTIVE
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 study was to evaluate the role of biliary phospholipids in dietary fat absorption in vivo by using mice homozygous or heterozygous for disruption of the Mdr2 gene (Mdr2((-/-)), Mdr2((+/-))) and control (Mdr2((+/+))) mice. Mdr2((-/-)) mice do not secrete phospholipids and cholesterol into bile, and bile salt secretion is not impaired. Mdr2((+/-)) mice show only impaired (-40%) phospholipid secretion.


METHODS
Methods included an analysis of time dependency of intestinal uptake and plasma appearance of intragastrically administered (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 response" of plasma triglycerides could be partially restored in Mdr2((-/-)) mice by intraduodenal infusion of whole rat bile. After intragastric [(3)H]triolein administration in Triton WR1339-pretreated animals, the appearance of (3)H-triglycerides in plasma was reduced by 70% in Mdr2((-/-)) compared with Mdr2((+/+)) mice, excluding accelerated lipolysis as the cause of defective triglyceride response in Mdr2((-/-)) mice. (3)H-triglycerides accumulated in enterocytes in Mdr2((-/-)) mice. Surprisingly, the efficacy of fat 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 (all >95%).


CONCLUSIONS
The results show that biliary lipid secretion is necessary for postprandial appearance in plasma of chylomicrons in vivo but not for quantitative absorption of dietary lipids.
Voshol
P J
PJ
Groningen Institute for Drug Studies, Center for Liver, Digestive, and Metabolic Diseases, University Hospital Groningen, Groningen, The Netherlands. p.j.voshol@med.rug.nl
Minich
D M
DM
Havinga
R
R
Elferink
R P
RP
Verkade
H J
HJ
Groen
A K
AK
Kuipers
F
F
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001646:Bile / Q000502:physiology*; D002914:Chylomicrons / Q000096:biosynthesis* / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D007408:Intestinal Absorption; D051379:Mice; D018345:Mice, Knockout; D000069463:Olive Oil; D010938:Plant Oils / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000494:pharmacology; D019518:Postprandial Period; D051381:Rats; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D014316:Tritium
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D002914:Chylomicrons; D004041:Dietary Fats; D000069463:Olive Oil; D010938:Plant Oils; D014280:Triglycerides; D014316:Tritium; D011092:Polyethylene Glycols; C095122:multidrug resistance protein 3; C016811:tyloxapol