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: Linda S Zhang, Min Xu, Qing Yang, Robert O Ryan, Philip Howles, Patrick Tso
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 308 Issue 7 Pg. G634-42 (Apr 01 2015) ISSN: 1522-1547 [Electronic] United States
• PMID: 25617349 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Apoa5 protein, mouse
• Apolipoprotein A-V
• Apolipoproteins
• Chylomicrons
• Triolein
• Cholesterol

Topics

• Administration, Oral
• Animals
• Apolipoprotein A-V
• Apolipoproteins (deficiency, genetics)
• Cholesterol (administration & dosage, metabolism)
• Chylomicrons (metabolism)
• Disease Models, Animal
• Duodenum (metabolism)
• Fistula (genetics, metabolism)
• Intestinal Absorption
• Lymph (metabolism)
• Lymphatic Diseases (genetics, metabolism)
• Lymphatic System (metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Postprandial Period
• Time Factors
• Triolein (administration & dosage, metabolism)
• Up-Regulation