Apolipoprotein A-V deficiency enhances chylomicron production in lymph fistula mice.

Zhang LS, Xu M, Yang Q, Ryan RO, Howles P, Tso P
Am J Physiol Gastrointest Liver Physiol. 2015 308 (7): G634-42

PMID: 25617349 · PMCID: PMC4385892 · DOI:10.1152/ajpgi.00339.2014

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.

Copyright © 2015 the American Physiological Society.

MeSH Terms (20)

Administration, Oral Animals Apolipoprotein A-V Apolipoproteins Cholesterol Chylomicrons Disease Models, Animal Duodenum Fistula Intestinal Absorption Lymph Lymphatic Diseases Lymphatic System Male Mice, Inbred C57BL Mice, Knockout Postprandial Period Time Factors Triolein Up-Regulation

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