Increased intestinal lipid absorption caused by Ire1β deficiency contributes to hyperlipidemia and atherosclerosis in apolipoprotein E–deficient mice

J Iqbal, J Queiroz, Y Li, XC Jiang, D Ron… - Circulation …, 2012 - Am Heart Assoc
J Iqbal, J Queiroz, Y Li, XC Jiang, D Ron, MM Hussain
Circulation research, 2012Am Heart Assoc
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 …
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.
Am Heart Assoc