title: Is apolipoprotein A-IV rate limiting in the intestinal transport and absorption of triglyceride?
abstract: Apolipoprotein A-IV (apoA-IV) is synthesized by the intestine and secreted when dietary fat is absorbed and transported into lymph associated with chylomicrons. We have recently demonstrated that loss of apoA-IV increases chylomicron size and delays its clearance from the blood. There is still uncertainty, however, about the precise role of apoA-IV on the transport of dietary fat from the intestine into the lymph. ApoA-IV knockout (KO) mice do not have a gross defect in dietary lipid absorption, as measured by oral fat tolerance and fecal fat measurements. Here, using the in vivo lymph fistula mouse model, we show that the cumulative secretion of triglyceride (TG) into lymph in apoA-IV KO mice is very similar to that of wild-type (WT) mice. However, the apoA-IV KO mice do have subtle changes in TG accumulation in the intestinal mucosa during a 6-h continuous, but not bolus, infusion of lipid. There are no changes in the ratio of esterified to free fatty acids in the intestinal mucosa of the apoA-IV KO, however. When we extended these findings, by giving a higher dose of lipid (6 μmol/h) and for a longer infusion period (8 h), we found no effect of apoA-IV KO on intestinal TG absorption. This higher lipid infusion most certainly stresses the intestine, as we see a drastically lower absorption of TG (in both WT and KO mice); however, the loss of A-IV does not exacerbate this effect. This supports our hypothesis that apoA-IV is not required for TG absorption in the intestine. Our data suggest that the mechanisms by which the apoA-IV KO intestine responds to intestinal lipid may not be different from their WT counterparts. We conclude that apoA-IV is not required for normal lymphatic transport of TG.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237, USA. alison.kohan@uc.edu
authors.forename: Alison B
authors.initials: AB
authors.lastname: Kohan
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.forename: Abbey E
authors.initials: AE
authors.lastname: Vandersall
authors.forename: Sarah
authors.initials: S
authors.lastname: Huesman
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Danwen
authors.initials: D
authors.lastname: Lou
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005402:Fistula; D007263:Infusions, Parenteral; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008055:Lipids / Q000008:administration & dosage; D008196:Lymph / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism*
chemical_list: D001054:Apolipoproteins A; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D014280:Triglycerides; C022205:apolipoprotein A-IV
keywords: apolipoprotein A-IV, chylomicron; intestinal lipid transport; lymph fistula mouse model