Increased Intestinal Lipid Absorption Caused by Ire1β Deficiency Contributes to Hyperlipidemia and Atherosclerosis in Apolipoprotein E–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, have development of 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.
- Received January 5, 2012.
- Revision received April 13, 2012.
- Accepted April 26, 2012.
- © 2012 American Heart Association, Inc.