Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis
Conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA) by autotaxin, a secreted phospholipase D, is a major pathway for producing LPA. We previously reported that feeding Ldlr−/− mice standard mouse chow supplemented with unsaturated LPA or lysophosphatidylcholine qualitatively mimicke...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523000433 |
| _version_ | 1797822143004672000 |
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| author | Arnab Chattopadhyay Pallavi Mukherjee Dawoud Sulaiman Huan Wang Victor Girjalva Nasrin Dorreh Jonathan P. Jacobs Samuel Delk Wouter H. Moolenaar Mohamad Navab Srinivasa T. Reddy Alan M. Fogelman |
| author_facet | Arnab Chattopadhyay Pallavi Mukherjee Dawoud Sulaiman Huan Wang Victor Girjalva Nasrin Dorreh Jonathan P. Jacobs Samuel Delk Wouter H. Moolenaar Mohamad Navab Srinivasa T. Reddy Alan M. Fogelman |
| author_sort | Arnab Chattopadhyay |
| collection | DOAJ |
| description | Conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA) by autotaxin, a secreted phospholipase D, is a major pathway for producing LPA. We previously reported that feeding Ldlr−/− mice standard mouse chow supplemented with unsaturated LPA or lysophosphatidylcholine qualitatively mimicked the dyslipidemia and atherosclerosis induced by feeding a Western diet (WD). Here, we report that adding unsaturated LPA to standard mouse chow also increased the content of reactive oxygen species and oxidized phospholipids (OxPLs) in jejunum mucus. To determine the role of intestinal autotaxin, enterocyte-specific Ldlr−/−/Enpp2 KO (intestinal KO) mice were generated. In control mice, the WD increased enterocyte Enpp2 expression and raised autotaxin levels. Ex vivo, addition of OxPL to jejunum from Ldlr−/− mice on a chow diet induced expression of Enpp2. In control mice, the WD raised OxPL levels in jejunum mucus and decreased gene expression in enterocytes for a number of peptides and proteins that affect antimicrobial activity. On the WD, the control mice developed elevated levels of lipopolysaccharide in jejunum mucus and plasma, with increased dyslipidemia and increased atherosclerosis. All these changes were reduced in the intestinal KO mice. We conclude that the WD increases the formation of intestinal OxPL, which i) induce enterocyte Enpp2 and autotaxin resulting in higher enterocyte LPA levels; that ii) contribute to the formation of reactive oxygen species that help to maintain the high OxPL levels; iii) decrease intestinal antimicrobial activity; and iv) raise plasma lipopolysaccharide levels that promote systemic inflammation and enhance atherosclerosis. |
| first_indexed | 2024-03-13T10:03:33Z |
| format | Article |
| id | doaj.art-c456bf32fd6f45f5a462ebc2070084da |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-03-13T10:03:33Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-c456bf32fd6f45f5a462ebc2070084da2023-05-23T04:20:37ZengElsevierJournal of Lipid Research0022-22752023-05-01645100370Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosisArnab Chattopadhyay0Pallavi Mukherjee1Dawoud Sulaiman2Huan Wang3Victor Girjalva4Nasrin Dorreh5Jonathan P. Jacobs6Samuel Delk7Wouter H. Moolenaar8Mohamad Navab9Srinivasa T. Reddy10Alan M. Fogelman11Division of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USADivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USADivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USADivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USADivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USADivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USAThe Vatche and Tamar Manoukian Division of Digestive Diseases, Fielding School of Public Health, University of California, Los Angeles, CA, USA; UCLA Microbiome Center, Fielding School of Public Health, University of California, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA and the Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Administration Greater Los Angeles Healthcare System Los Angeles, Fielding School of Public Health, University of California, Los Angeles, CA, USADivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USA; Molecular Toxicology Interdepartmental Degree Program, Fielding School of Public Health, University of California, Los Angeles, CA, USADivision of Biochemistry, Netherlands Cancer Institute, Amsterdam, the NetherlandsDivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USADivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USA; Molecular Toxicology Interdepartmental Degree Program, Fielding School of Public Health, University of California, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, Fielding School of Public Health, University of California, Los Angeles, CA, USA; For correspondence: Srinivasa T. ReddyDivision of Cardiology, Department of Medicine, Fielding School of Public Health, University of California, Los Angeles, CA, USAConversion of lysophosphatidylcholine to lysophosphatidic acid (LPA) by autotaxin, a secreted phospholipase D, is a major pathway for producing LPA. We previously reported that feeding Ldlr−/− mice standard mouse chow supplemented with unsaturated LPA or lysophosphatidylcholine qualitatively mimicked the dyslipidemia and atherosclerosis induced by feeding a Western diet (WD). Here, we report that adding unsaturated LPA to standard mouse chow also increased the content of reactive oxygen species and oxidized phospholipids (OxPLs) in jejunum mucus. To determine the role of intestinal autotaxin, enterocyte-specific Ldlr−/−/Enpp2 KO (intestinal KO) mice were generated. In control mice, the WD increased enterocyte Enpp2 expression and raised autotaxin levels. Ex vivo, addition of OxPL to jejunum from Ldlr−/− mice on a chow diet induced expression of Enpp2. In control mice, the WD raised OxPL levels in jejunum mucus and decreased gene expression in enterocytes for a number of peptides and proteins that affect antimicrobial activity. On the WD, the control mice developed elevated levels of lipopolysaccharide in jejunum mucus and plasma, with increased dyslipidemia and increased atherosclerosis. All these changes were reduced in the intestinal KO mice. We conclude that the WD increases the formation of intestinal OxPL, which i) induce enterocyte Enpp2 and autotaxin resulting in higher enterocyte LPA levels; that ii) contribute to the formation of reactive oxygen species that help to maintain the high OxPL levels; iii) decrease intestinal antimicrobial activity; and iv) raise plasma lipopolysaccharide levels that promote systemic inflammation and enhance atherosclerosis.http://www.sciencedirect.com/science/article/pii/S0022227523000433lysophospholipase Dlysophosphatidic acidatherosclerosisoxidized phospholipidssmall intestineapolipoprotein A-I mimetic peptides |
| spellingShingle | Arnab Chattopadhyay Pallavi Mukherjee Dawoud Sulaiman Huan Wang Victor Girjalva Nasrin Dorreh Jonathan P. Jacobs Samuel Delk Wouter H. Moolenaar Mohamad Navab Srinivasa T. Reddy Alan M. Fogelman Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis Journal of Lipid Research lysophospholipase D lysophosphatidic acid atherosclerosis oxidized phospholipids small intestine apolipoprotein A-I mimetic peptides |
| title | Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis |
| title_full | Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis |
| title_fullStr | Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis |
| title_full_unstemmed | Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis |
| title_short | Role of enterocyte Enpp2 and autotaxin in regulating lipopolysaccharide levels, systemic inflammation, and atherosclerosis |
| title_sort | role of enterocyte enpp2 and autotaxin in regulating lipopolysaccharide levels systemic inflammation and atherosclerosis |
| topic | lysophospholipase D lysophosphatidic acid atherosclerosis oxidized phospholipids small intestine apolipoprotein A-I mimetic peptides |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523000433 |
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