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.
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.
Authors: A Bertolotti; X Wang; I Novoa; R Jungreis; K Schlessinger; J H Cho; A B West; D Ron Journal: J Clin Invest Date: 2001-03 Impact factor: 14.808
Authors: John D Douglass; Nashmia Malik; Su-Hyoun Chon; Kevin Wells; Yin Xiu Zhou; Andrew S Choi; Laurie B Joseph; Judith Storch Journal: Front Physiol Date: 2012-02-24 Impact factor: 4.566
Authors: Mohamad Navab; Arnab Chattopadhyay; Greg Hough; David Meriwether; Spencer I Fogelman; Alan C Wagner; Victor Grijalva; Feng Su; G M Anantharamaiah; Lin H Hwang; Kym F Faull; Srinivasa T Reddy; Alan M Fogelman Journal: J Lipid Res Date: 2015-02-02 Impact factor: 5.922