Abstract 504: Increased Intestinal Lipid Absorption Caused by Ire1β Deficiency Contributes to Hyperlipidemia and Atherosclerosis in ApoE-Deficient Mice
Rationale: High fasting serum lipid levels are significant risk factors for atherosclerosis. However, the contributions of postprandial excursions in serum lipoproteins to atherogenesis are less well characterized.
Objective: This study aims to delineate whether changes in intestinal lipid absorption associated with loss of inositol requiring enzyme 1β (Ire1β) would affect the development of hyperlipidemia and atherosclerosis in Apoe-/- mice.
Methods and Results: We used Ire1β deficient mice to assess the contribution of intestinal lipid absorption to atherosclerosis. Here we show that Ire1b-/-/Apoe-/- mice contain higher levels of intestinal microsomal triglyceride transfer protein, absorb more lipids, develop hyperlipidemia, and have higher levels of atherosclerotic plaques compared to Apoe-/- mice when fed chow and western diets. In contrast, plasma cytokines were similar in Ire1b-/-/Apoe-/- and Apoe-/- mice.
Conclusions: These studies indicate that Ire1β regulates intestinal lipid absorption and that increased intestinal lipoprotein production contributes to atherosclerosis.
- © 2012 by American Heart Association, Inc.