ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
PON3 knockout mice are susceptible to obesity, gallstone formation, and atherosclerosis.
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Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28citing papers in PubMed
1.9field-weighted citation impact, top 16% of its field
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
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- A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease.Antioxidants (Basel, Switzerland) · 2022Review
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- Paraoxonase 3 functions as a chaperone to decrease functional expression of the epithelial sodium channel.The Journal of biological chemistry · 2020Article
- Paraoxonase 3: Structure and Its Role in Pathophysiology of Coronary Artery Disease.Biomolecules · 2019Review
- Iron deficiency in worsening heart failure is associated with reduced estimated protein intake, fluid retention, inflammation, and antiplatelet use.European heart journal · 2019Observational
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Authors and funding
15 authors at 7 institutions in 4 countries.
Diana M Shih*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland dshih@mednet.ucla.edu.
Janet M Yu*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Laurent Vergnes*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Nassim Dali-Youcef*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Matthew D Champion*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Asokan Devarajan*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Peixiang Zhang*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Lawrence W Castellani*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
David N Brindley*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Carole Jamey*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Johan Auwerx*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Srinivasa T Reddy*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
David A Ford*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Karen Reue*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Aldons J Lusis*Division of Cardiology, Department of Medicine, Department of Microbiology, Immunology, and Molecular Genetics, Department of Human Genetics, Department of Molecular and Medical Pharmacology, and Department of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA; IGBMC, Illkirch and Hôpitaux Universitaires de Strasbourg, and **Laboratoire de Toxicologie, Universitaires de Strasbourg, Strasbourg, France; Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research, St. Louis University School of Medicine, St. Louis, Missouri, USA; University of Alberta, Edmonton, Alberta, Canada; and Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
University of California, Los Angeles · USLos Angeles Medical Center · USUniversity of Alberta · CAÉcole Polytechnique Fédérale de Lausanne · CHHôpitaux Universitaires de Strasbourg · FRInstitut de génétique et de biologie moléculaire et cellulaire · FRSaint Louis University · US
Funding
ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2MSystems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 1985 to 2019
$50.2MThe role of PON2 and PON3 proteins in AtherosclerosisR01HL071776 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REDDY, SRINIVASA T. · 2003 to 2017
$4.8MPlasmalogen-derived bioactive lipids in atherosclerosisR01HL074214 · NHLBI · SAINT LOUIS UNIVERSITY · PI FORD, DAVID A. · 2004 to 2014
$2.8MTSQ QUANTUM ESI-MS SURVEYOR BUNDLE: RENAL, HEART, RETINAL, &LUNG DISEASESS10RR019232 · NCRR · SAINT LOUIS UNIVERSITY · PI FORD, DAVID A. · 2004 to 2004
$339kXF24-3 Extracellular Flux AnalyzerS10RR026744 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 2010 to 2010
$168kNCRR NIH HHS RR019232NCRR NIH HHS S10 RR019232NCRR NIH HHS S10 RR026744NCRR NIH HHS S10RR026744NHLBI NIH HHS 2 RO1 HL71776NHLBI NIH HHS HL030568-26A1NHLBI NIH HHS NIH P01 HL028481NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R01 HL071776NHLBI NIH HHS R01 HL074214
Abstract
We report the engineering and characterization of paraoxonase-3 knockout mice (Pon3KO). The mice were generally healthy but exhibited quantitative alterations in bile acid metabolism and a 37% increased body weight compared to the wild-type mice on a high fat diet. PON3 was enriched in the mitochondria-associated membrane fraction of hepatocytes. PON3 deficiency resulted in impaired mitochondrial respiration, increased mitochondrial superoxide levels, and increased hepatic expression of inflammatory genes. PON3 deficiency did not influence atherosclerosis development on an apolipoprotein E null hyperlipidemic background, but it did lead to a significant 60% increase in atherosclerotic lesion size in Pon3KO mice on the C57BL/6J background when fed a cholate-cholesterol diet. On the diet, the Pon3KO had significantly increased plasma intermediate-density lipoprotein/LDL cholesterol and bile acid levels. They also exhibited significantly elevated levels of hepatotoxicity markers in circulation, a 58% increase in gallstone weight, a 40% increase in hepatic cholesterol level, and increased mortality. Furthermore, Pon3KO mice exhibited decreased hepatic bile acid synthesis and decreased bile acid levels in the small intestine compared with wild-type mice. Our study suggests a role for PON3 in the metabolism of lipid and bile acid as well as protection against atherosclerosis, gallstone disease, and obesity.
Indexed as
AnimalsApolipoproteins EAryldialkylphosphataseAtherosclerosisBile Acids and SaltsChemokine CCL2Cholesterol, DietaryCholic AcidDietDisease Models, AnimalFemaleGallstonesGene ExpressionGenetic Predisposition to DiseaseInflammation MediatorsInterleukin-6Apolipoproteins EAryldialkylphosphataseBile Acids and SaltsCcl2 protein, mouseChemokine CCL2Cholesterol, DietaryCholic AcidInflammation MediatorsInterleukin-6PON3 protein, mousebile acidcholesterolhyperlipidemiamitochondriamitochondria-associated membrane
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