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

Circulation Research
Jahangir IqbalM Mahmood Hussain

Abstract

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. 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. 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. These studies indicate that Ire1β regulates intestinal lipid absorption and that increased intestinal lipoprotein production contributes to atherosclerosis.

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Citations

Jan 11, 2014·Clinical Lipidology·M Mahmood HussainSarah Abu-Merhi
Feb 4, 2015·Journal of Lipid Research·Mohamad NavabAlan M Fogelman
Sep 10, 2013·Circulation·Xiaoyue PanM Mahmood Hussain
Nov 15, 2013·IUBMB Life·Víctor Hugo CornejoClaudio Hetz
Jul 2, 2016·The Journal of Biological Chemistry·Sara IraniM Mahmood Hussain
Apr 9, 2019·Journal of Cellular and Molecular Medicine·Guozhu YeSijun Dong

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