Increased intestinal lipid absorption caused by ire1β deficiency contributes to hyperlipidemia and atherosclerosis in apolipoprotein e-deficient mice

Abstract

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, exhibit hyperlipidemia, and have higher levels of atherosclerotic plaques compared with Apoe -/- mice when fed chow and western diets. Conclusions: These studies indicate that Ire1β regulates intestinal lipid absorption and that increased intestinal lipoprotein production contributes to atherosclerosis. © 2012 American Heart Association, Inc.