Abstract 388: Apolipoprotein A-V Deficiency in Mice Results In Increased Triglyceride and Cholesterol Absorption
Elevated plasma triglycerides constitute an independent risk factor for coronary heart disease. Discovered in 2001, apolipoprotein A-V (apoA-V) was found inversely proportional to plasma triglycerides (TG). Synthesized only in the liver, apoA-V exists in very low concentrations in the plasma (~10,000 fold lower than apoA-I). While apoA-V is proposed to enhance hydrolysis and reduce hepatic production of TG-rich lipoproteins, the role of apoA-V on intestinal lipid absorption has not been investigated. The aim of this study is to examine the effects of apoA-V deficiency on intestinal lipid absorption in chow-fed mice. Since mice lacking functional apoA-V have drastically elevated plasma TG, we hypothesize that apoA-V deficiency in mice elevates the lymphatic output of TG after a lipid meal. Using apoA-V knockout (n=8) and wildtype (n=8) control mice, we employed the conscious lymph fistula model to examine the transport of dietary TG and cholesterol into the lymph during a continuous lipid infusion. Interestingly, apoA-V knockout mice displayed a 2-fold elevation in dietary TG (P<0.001) and a 3-fold elevation in dietary cholesterol (P<0.001) transport into the lymph compared to wildtype mice, suggesting that a loss of apoA-V enhances transport across the enterocyte. However, apoA-V knockout mice displayed a 2-fold reduction (P<0.05) in dietary TG accumulated in the intestinal mucosa while there was no difference in the mucosal accumulation of dietary cholesterol between apoA-V knockout and wildtype mice, suggesting that apoA-V affected TG and cholesterol transport in the enterocyte differently. We conclude apoA-V deficiency results in increased TG and cholesterol absorption in mice, and therefore plays a previously unknown role in intestinal lipid absorption.
- © 2013 by American Heart Association, Inc.