title: Lymphatic chylomicron size is inversely related to biliary phospholipid secretion in mice.
abstract: Biliary phospholipids (PL) stimulate dietary fat absorption by facilitating intraluminal lipid solubilization and by providing surface components for chylomicron (CM) assembly. Impaired hepatic PL availability induces secretion of large very-low-density lipoproteins, but it is unclear whether CM size depends on biliary PL availability. Biliary PL secretion is absent in multidrug resistance protein 2-deficient (Mdr2(-/-)) mice, whereas it is strongly increased in essential fatty acid (EFA)-deficient mice. We investigated lymphatic CM size and composition in mice with absent (Mdr2(-/-)) or enhanced (EFA deficient) biliary PL secretion and in their respective controls under basal conditions and during enteral lipid administration. EFA deficiency was induced by feeding mice a high-fat, EFA-deficient diet for 8 wk. Lymph was collected by mesenteric lymph duct cannulation with or without intraduodenal lipid administration. Lymph was collected in 30-min fractions for up to 4 h, and lymphatic lipoprotein size was determined by dynamic light-scattering techniques. Lymph lipoprotein subfractions were isolated by ultracentrifugation, and lipid composition was measured. Lymphatic CMs were significantly larger in Mdr2(-/-) mice than in Mdr2(+/+) controls either without (+50%) or with (+25%) enteral lipid administration, and molar core-surface ratios were increased [triglyceride (TG)-to-PL ratio: 4.4 +/- 1.4 in Mdr2(-/-) mice vs. 2.7 +/- 0.8 in Mdr2(+/+) mice, P < 0.001]. In contrast, EFA-deficient mice secreted lipoproteins into lymph that were significantly smaller than in EFA-sufficient controls (173 +/- 32 vs. 236 +/- 47 nm), with correspondingly decreased core-surface ratios (TG-to-PL ratio: 3.0 +/- 1.0 in EFA-deficient mice vs. 6.0 +/- 1.9 in EFA-sufficient mice, P < 0.001). CM size increased during fat absorption in both EFA-deficient and EFA-sufficient mice, but the difference between the groups persisted. In conclusion, the present results strongly suggest that the availability of biliary PL is a major determinant of the size of intestinally produced lipoproteins both under basal conditions and during lipid absorption. Altered CM size may have physiological consequences for postprandial CM processing.
authors.affiliation: Pediatric Gastroenterology, Department of Pediatrics, Groningen University Institute for Drug Exploration, University Medical Center Groningen, University of Groningen, The Netherlands. a.werner@med.umcg.nl
authors.forename: Anniek
authors.initials: A
authors.lastname: Werner
authors.forename: Rick
authors.initials: R
authors.lastname: Havinga
authors.forename: Frank
authors.initials: F
authors.lastname: Perton
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000378:metabolism*; D002914:Chylomicrons / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D005228:Fatty Acids, Essential / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism*; D051379:Mice; D010743:Phospholipids / Q000378:metabolism*; D013223:Statistics as Topic
chemical_list: D002914:Chylomicrons; D005228:Fatty Acids, Essential; D010743:Phospholipids