ArticleCell metabolism2014
The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism.
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Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54citing papers in PubMed
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54 citing papers in PubMed, 115 citations in OpenAlex.
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Authors and funding
42 authors at 16 institutions in 9 countries.
Egon DemetzDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Andrea SchrollDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Kristina AuerDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Christiane HeimDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Josef R PatschDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Philipp EllerDepartment of Internal Medicine, Angiology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Markus TheurlDepartment of Internal Medicine III, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Igor TheurlDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Milan TheurlDepartment of Ophthalmology and Optometry, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Markus SeifertDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Daniela LenerDepartment of Internal Medicine III, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Ursula StanzlDepartment of Internal Medicine III, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
David HaschkaDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Malte AsshoffDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Stefanie DichtlDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Manfred NairzDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Eva HuberDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Martin StadlingerDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Alexander R MoschenDepartment of Internal Medicine I, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Xiaorong LiDepartment of Pharmacology, Capital Medical University, Number 10 Xitoutiao, You An Men, 100069 Beijing, China.
Petra PallweberDepartment of Pediatrics II, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Hubert ScharnaglClinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Tatjana StojakovicClinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Winfried MärzClinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Department of Internal Medicine, Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; Synlab Academy, Harrlachweg 1, 68163 Mannheim, Germany.
Marcus E KleberDepartment of Internal Medicine, Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Katia GarlaschelliCenter for the Study of Atherosclerosis, Bassini Hospital, via Gorki 50, 20092 Cinisello Balsamo Milan, Italy.
Patrizia UboldiDepartment of Pharmacological and Biomolecular Sciences, Università Degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy.
Alberico L CatapanoDepartment of Pharmacological and Biomolecular Sciences, Università Degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy; IRCCS Multimedica, via Milanese 300, 20099 Sesto San Giovanni Milan, Italy.
Frans StellaardDepartment of Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
Mats RudlingDepartment of Medicine and Department of Biosciences and Nutrition, Karolinska Institute at Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
Keiji KubaDepartment of Biological Informatics and Experimental Therapeutics, Graduate School of Medicine, Akita University, 1-1 Tegata Gakuen-machi, 010-8502 Akita City, Japan.
Yumiko ImaiDepartment of Biological Informatics and Experimental Therapeutics, Graduate School of Medicine, Akita University, 1-1 Tegata Gakuen-machi, 010-8502 Akita City, Japan.
Makoto AritaDepartment of Health Chemistry, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8654 Tokyo, Japan.
John D SchuetzDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS313, Memphis, TN 38105, USA.
Peter P PramstallerCenter for Biomedicine, European Academy Bozen/Bolzano (EURAC), Drususallee 1, 39100 Bolzano, Italy-Affiliated Institute of the University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany.
Uwe J F TietgeDepartment of Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
Michael TraunerHans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Giuseppe D NorataCenter for the Study of Atherosclerosis, Bassini Hospital, via Gorki 50, 20092 Cinisello Balsamo Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Università Degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy; The Blizard Institute, Centre for Diabetes, Barts and The London School of Medicine & Dentistry, Queen Mary University, 4 Newark Street, E1 2AT London, UK.
Thierry ClaudelHans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Andrew A HicksCenter for Biomedicine, European Academy Bozen/Bolzano (EURAC), Drususallee 1, 39100 Bolzano, Italy-Affiliated Institute of the University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany.
Guenter WeissDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: guenter.weiss@i-med.ac.at.
Ivan TancevskiDepartment of Internal Medicine VI, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: ivan.tancevski@i-med.ac.at.
Innsbruck Medical University · ATMedical University of Graz · ATAkita University · JPMedical University of Vienna · ATUniversity of Groningen · NLUniversity of Milan · ITCapital Medical University · CNEurac Research · ITHeidelberg University · DEKarolinska Institutet · SEMultiMedica · ITOspedale Bassini · ITSt. Jude Children's Research Hospital · USThe University of Tokyo · JPUniversity Hospital Heidelberg · DEUniversity of Lübeck · DE
Funding
Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MAustrian Science Fund FWF P 23853Austrian Science Fund FWF TRP 188NCI NIH HHS P30 CA021765Telethon GGP13002
Abstract
Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By combining data from a GWAS screening in >100,000 individuals of European ancestry, mediator lipidomics, and functional validation studies in mice, we identify the AA metabolome as an important regulator of cholesterol homeostasis. Pharmacological modulation of AA metabolism by aspirin induced hepatic generation of leukotrienes (LTs) and lipoxins (LXs), thereby increasing hepatic expression of the bile salt export pump Abcb11. Induction of Abcb11 translated in enhanced reverse cholesterol transport, one key function of HDL. Further characterization of the bioactive AA-derivatives identified LX mimetics to lower plasma LDL-C. Our results define the AA metabolomeasconserved regulator of cholesterol metabolism, and identify AA derivatives as promising therapeutics to treat cardiovascular disease in humans.
Indexed as
MetabolomeAnimalsAnti-Inflammatory Agents, Non-SteroidalArachidonate 5-LipoxygenaseArachidonic AcidAspirinAtherosclerosisBile Acids and SaltsCells, CulturedCholesterolCholesterol, HDLHumansLeukotrienesLiverMiceMice, Inbred C57BLALOX5 protein, humanAnti-Inflammatory Agents, Non-SteroidalArachidonate 5-LipoxygenaseArachidonic AcidAspirinBile Acids and SaltsCholesterolCholesterol, HDLLeukotrienes
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