Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis
We previously reported that i) a Western diet increased levels of unsaturated lysophosphatidic acid (LPA) in small intestine and plasma of LDL receptor null (LDLR−/−) mice, and ii) supplementing standard mouse chow with unsaturated (but not saturated) LPA produced dyslipidemia and inflammation. Here...
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Format: | Article |
Language: | English |
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Elsevier
2015-04-01
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Series: | Journal of Lipid Research |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520355681 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis Journal of Lipid Research lysophosphatidylcholine 6F peptide apolipoprotein A-I mimetic peptides genetically engineered tomato plants |
author_facet |
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 |
author_sort |
Mohamad Navab |
title |
Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis |
title_short |
Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis |
title_full |
Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis |
title_fullStr |
Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis |
title_full_unstemmed |
Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis |
title_sort |
source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2015-04-01 |
description |
We previously reported that i) a Western diet increased levels of unsaturated lysophosphatidic acid (LPA) in small intestine and plasma of LDL receptor null (LDLR−/−) mice, and ii) supplementing standard mouse chow with unsaturated (but not saturated) LPA produced dyslipidemia and inflammation. Here we report that supplementing chow with unsaturated (but not saturated) LPA resulted in aortic atherosclerosis, which was ameliorated by adding transgenic 6F tomatoes. Supplementing chow with lysophosphatidylcholine (LysoPC) 18:1 (but not LysoPC 18:0) resulted in dyslipidemia similar to that seen on adding LPA 18:1 to chow. PF8380 (a specific inhibitor of autotaxin) significantly ameliorated the LysoPC 18:1-induced dyslipidemia. Supplementing chow with LysoPC 18:1 dramatically increased the levels of unsaturated LPA species in small intestine, liver, and plasma, and the increase was significantly ameliorated by PF8380 indicating that the conversion of LysoPC 18:1 to LPA 18:1 was autotaxin dependent. Adding LysoPC 18:0 to chow increased levels of LPA 18:0 in small intestine, liver, and plasma but was not altered by PF8380 indicating that conversion of LysoPC 18:0 to LPA 18:0 was autotaxin independent. We conclude that i) intestinally derived unsaturated (but not saturated) LPA can cause atherosclerosis in LDLR−/− mice, and ii) autotaxin mediates the conversion of unsaturated (but not saturated) LysoPC to LPA. |
topic |
lysophosphatidylcholine 6F peptide apolipoprotein A-I mimetic peptides genetically engineered tomato plants |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520355681 |
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doaj-9ccc1c76f4704629a380d57e471e33792021-04-28T06:00:22ZengElsevierJournal of Lipid Research0022-22752015-04-01564871887Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosisMohamad Navab0Arnab Chattopadhyay1Greg Hough2David Meriwether3Spencer I. Fogelman4Alan C. Wagner5Victor Grijalva6Feng Su7G.M. Anantharamaiah8Lin H. Hwang9Kym F. Faull10Srinivasa T. Reddy11Alan M. Fogelman12Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736To whom correspondence should be addressed; Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736; Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736; To whom correspondence should be addressedDepartment of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736We previously reported that i) a Western diet increased levels of unsaturated lysophosphatidic acid (LPA) in small intestine and plasma of LDL receptor null (LDLR−/−) mice, and ii) supplementing standard mouse chow with unsaturated (but not saturated) LPA produced dyslipidemia and inflammation. Here we report that supplementing chow with unsaturated (but not saturated) LPA resulted in aortic atherosclerosis, which was ameliorated by adding transgenic 6F tomatoes. Supplementing chow with lysophosphatidylcholine (LysoPC) 18:1 (but not LysoPC 18:0) resulted in dyslipidemia similar to that seen on adding LPA 18:1 to chow. PF8380 (a specific inhibitor of autotaxin) significantly ameliorated the LysoPC 18:1-induced dyslipidemia. Supplementing chow with LysoPC 18:1 dramatically increased the levels of unsaturated LPA species in small intestine, liver, and plasma, and the increase was significantly ameliorated by PF8380 indicating that the conversion of LysoPC 18:1 to LPA 18:1 was autotaxin dependent. Adding LysoPC 18:0 to chow increased levels of LPA 18:0 in small intestine, liver, and plasma but was not altered by PF8380 indicating that conversion of LysoPC 18:0 to LPA 18:0 was autotaxin independent. We conclude that i) intestinally derived unsaturated (but not saturated) LPA can cause atherosclerosis in LDLR−/− mice, and ii) autotaxin mediates the conversion of unsaturated (but not saturated) LysoPC to LPA.http://www.sciencedirect.com/science/article/pii/S0022227520355681lysophosphatidylcholine6F peptideapolipoprotein A-I mimetic peptidesgenetically engineered tomato plants |