title: Apolipoprotein A-V deficiency enhances chylomicron production in lymph fistula mice.
abstract: Apolipoprotein A-V (apoA-V), a liver-synthesized apolipoprotein discovered in 2001, strongly modulates fasting plasma triglycerides (TG). Little is reported on the effect of apoA-V on postprandial plasma TG, an independent predictor for atherosclerosis. Overexpressing apoA-V in mice suppresses postprandial TG, but mechanisms focus on increased lipolysis or clearance of remnant particles. Unknown is whether apoA-V suppresses the absorption of dietary lipids by the gut. This study examines how apoA-V deficiency affects the steady-state absorption and lymphatic transport of dietary lipids in chow-fed mice. Using apoA-V knockout (KO, n = 8) and wild-type (WT, n = 8) lymph fistula mice, we analyzed the uptake and lymphatic transport of lipids during a continuous infusion of an emulsion containing [(3)H]triolein and [(14)C]cholesterol. ApoA-V KO mice showed a twofold increase in (3)H (P < 0.001) and a threefold increase in (14)C (P < 0.001) transport into the lymph compared with WT. The increased lymphatic transport was accompanied by a twofold reduction (P < 0.05) in mucosal (3)H, suggesting that apoA-V KO mice more rapidly secreted [(3)H]TG out of the mucosa into the lymph. ApoA-V KO mice also produced chylomicrons more rapidly than WT (P < 0.05), as measured by the transit time of [(14)C]oleic acid from the intestinal lumen to lymph. Interestingly, apoA-V KO mice produced a steadily increasing number of chylomicron particles over time, as measured by lymphatic apoB output. The data suggest that apoA-V suppresses the production of chylomicrons, playing a previously unknown role in lipid metabolism that may contribute to the postprandial hypertriglyceridemia associated with apoA-V deficiency.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California zhangld@mail.uc.edu.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Zhang
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; and.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California.
authors.forename: Philip
authors.initials: P
authors.lastname: Howles
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000172:deficiency* / Q000235:genetics; D002784:Cholesterol / Q000008:administration & dosage / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism*; D005402:Fistula / Q000235:genetics / Q000378:metabolism*; D007408:Intestinal Absorption; D008196:Lymph / Q000378:metabolism*; D008206:Lymphatic Diseases / Q000235:genetics / Q000378:metabolism*; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019518:Postprandial Period; D013997:Time Factors; D014304:Triolein / Q000008:administration & dosage / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D002914:Chylomicrons; D014304:Triolein; D002784:Cholesterol
keywords: absorption; intestine