title: Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation.
abstract: Essential fatty acid (EFA) deficiency induces fat malabsorption, but the pathophysiological mechanism is unknown. Bile salts (BS) and EFA-rich biliary phospholipids affect dietary fat solubilization and chylomicron formation, respectively. We investigated whether altered biliary BS and/or phospholipid secretion mediate EFA deficiency-induced fat malabsorption in mice. Free virus breed (FVB) mice received EFA-containing (EFA(+)) or EFA-deficient (EFA(-)) chow for 8 wk. Subsequently, fat absorption, bile flow, and bile composition were determined. Identical dietary experiments were performed in multidrug resistance gene-2-deficient [Mdr2((-/-))] mice, secreting phospholipid-free bile. After 8 wk, EFA(-)-fed wild-type [Mdr2((+/+))] and Mdr2((-/-)) mice were markedly EFA deficient [plasma triene (20:3n-9)-to-tetraene (20:4n-6) ratio >0.2]. Fat absorption decreased (70.1 +/- 4.2 vs. 99.1 +/- 0.3%, P < 0.001), but bile flow and biliary BS secretion increased in EFA(-) mice compared with EFA(+) controls (4.87 +/- 0.36 vs. 2.87 +/- 0.29 microl x min(-1) x 100 g body wt(-1), P < 0.001, and 252 +/- 30 vs. 145 +/- 20 nmol x min(-1) x 100 g body wt(-1), P < 0.001, respectively). BS composition was similar in EFA(+)- and EFA(-)-fed mice. Similar to EFA(-) Mdr2((+/+)) mice, EFA(-) Mdr2((-/-)) mice developed fat malabsorption associated with twofold increase in bile flow and BS secretion. Fat malabsorption in EFA(-) mice is not due to impaired biliary BS or phospholipid secretion. We hypothesize that EFA deficiency affects intracellular processing of dietary fat by enterocytes.
authors.affiliation: Center for Liver, Digestive, and Metabolic Diseases, Pediatric Gastroenterology, Department of Pediatrics, University Hospital, 9700 RB Groningen, The Netherlands.
authors.forename: Anniek
authors.initials: A
authors.lastname: Werner
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Minich
authors.forename: Rick
authors.initials: R
authors.lastname: Havinga
authors.forename: Vincent
authors.initials: V
authors.lastname: Bloks
authors.forename: Harry
authors.initials: H
authors.lastname: Van Goor
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000172:deficiency / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000502:physiology*; D001647:Bile Acids and Salts / Q000378:metabolism; D001835:Body Weight; D002250:Carbon Radioisotopes; D053493:Cholestanetriol 26-Monooxygenase; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004041:Dietary Fats / Q000378:metabolism*; D004224:Diterpenes; D020895:Enterocytes / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005228:Fatty Acids, Essential / Q000008:administration & dosage / Q000172:deficiency*; D006720:Homozygote; D007700:Kinetics; D008099:Liver / Q000737:chemistry; D008286:Malabsorption Syndromes / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D019301:Oleic Acid / Q000097:blood; D010743:Phospholipids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012333:RNA, Messenger / Q000032:analysis; D000084562:Retinyl Esters; D013250:Steroid Hydroxylases / Q000235:genetics; D014304:Triolein / Q000032:analysis; D014316:Tritium; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D004041:Dietary Fats; D004224:Diterpenes; D005227:Fatty Acids; D005228:Fatty Acids, Essential; D010743:Phospholipids; D012333:RNA, Messenger; D000084562:Retinyl Esters; D014316:Tritium; D014801:Vitamin A; D014304:Triolein; C014794:retinol palmitate; D019301:Oleic Acid; D011092:Polyethylene Glycols; D003577:Cytochrome P-450 Enzyme System; C095122:multidrug resistance protein 3; D013250:Steroid Hydroxylases; D002790:Cholesterol 7-alpha-Hydroxylase; D053493:Cholestanetriol 26-Monooxygenase; C506832:Cyp27a1 protein, mouse; C016811:tyloxapol