Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism

    Access Status
    Open access via publisher
    Authors
    Demetz, E.
    Schroll, A.
    Auer, K.
    Heim, C.
    Patsch, J.
    Eller, P.
    Theurl, M.
    Theurl, I.
    Theurl, M.
    Seifert, M.
    Lener, D.
    Stanzl, U.
    Haschka, D.
    Asshoff, M.
    Dichtl, S.
    Nairz, M.
    Huber, E.
    Stadlinger, M.
    Moschen, A.
    Li, X.
    Pallweber, P.
    Scharnagl, H.
    Stojakovic, T.
    März, W.
    Kleber, M.
    Garlaschelli, K.
    Uboldi, P.
    Catapano, A.
    Stellaard, F.
    Rudling, M.
    Kuba, K.
    Imai, Y.
    Arita, M.
    Schuetz, J.
    Pramstaller, P.
    Tietge, U.
    Trauner, M.
    Norata, Giuseppe
    Claudel, T.
    Hicks, A.
    Weiss, G.
    Tancevski, I.
    Date
    2014
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Demetz, E. and Schroll, A. and Auer, K. and Heim, C. and Patsch, J. and Eller, P. and Theurl, M. et al. 2014. The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism. Cell Metabolism. 20 (5): pp. 787-798.
    Source Title
    Cell Metabolism
    DOI
    10.1016/j.cmet.2014.09.004
    ISSN
    1550-4131
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/55291
    Collection
    • Curtin Research Publications
    Abstract

    © 2014 The Authors. 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 metabolome as conserved regulator of cholesterol metabolism, and identify AA derivatives as promising therapeutics to treat cardiovascular disease in humans. Omega-6 polyunsaturated fatty acids, including arachidonic acid (AA), have beneficial cardiovascular effects. Demetz et al. show that Alox5, a key enzyme of the AA pathway, regulates cholesterol in humans. Modulation of the AA pathways genetically or pharmacologically, with aspirin or bioactive AA-mimetics influences cholesterol metabolism including reverse cholesterol transport.

    Related items

    Showing items related by title, author, creator and subject.

    • Hepatic iron loading in mice increases cholesterol biosynthesis
      Graham, Ross; Chua, A.; Carter, K.; Delima, R.; Johnstone, D.; Herbison, C.; Firth, M.; O'Leary, R.; Milward, E.; Olynyk, J.; Trinder, D. (2010)
      Iron and cholesterol are both essential metabolites in mammalian systems, and too much or too little of either can have serious clinical consequences. In addition, both have been associated with steatosis and its progression, ...
    • Nutritional and pharmacological regulation of cerebral capillary function
      Pallebage-Gamarallage, Menuka Madhavi Somapala (2012)
      Alzheimer’s disease (AD) is the most common cause of dementia pathologically characterised by neurovascular inflammation, extracellular proteinaceous deposits enriched in amyloid-β (Aβ) and formation of neurofibrillar ...
    • Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism.
      Caparrós-Martín, J.; Lareu, R.; Ramsay, J.; Peplies, J.; Jerry Reen, F.; Headlam, H.; Ward, Natalie; Croft, K.; Newsholme, P.; Hughes, J.; O'Gara, F. (2017)
      BACKGROUND: Statins are a class of therapeutics used to regulate serum cholesterol and reduce the risk of heart disease. Although statins are highly effective in removing cholesterol from the blood, their consumption has ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.