Fatty acids prevent Hypoxia-Inducible Factor 1α signalling in type 2 diabetes

Michael Dodd, Maria da Luz Sousa Fialho, Claudia N. Montes Aparico, Matthew Kerr, Kerstin N. Timm, Julian L. Griffin, Joost J.F.P. Luiken, Jan F.C. Glatz, Damian J Tyler, Lisa C Heather

    Research output: Contribution to journalArticlepeer-review

    64 Citations (Scopus)
    194 Downloads (Pure)

    Abstract

    • HIF-1α is activated following myocardial infarction, and is a critical transcription factor promoting survival in hypoxia.

    • Type 2 diabetes blunts HIF-1α activation in ischemia and downstream adaptation to hypoxia.

    • This effect is mediated by increased long-chain fatty acids, which prevent HIF-1α activation in hypoxia.

    • Succinate promotes HIF-1α activation by inhibiting the regulatory HIF hydroxylases. Fatty acids decrease succinate concentrations in hypoxia, by blocking increased glycolysis and malate-aspartate shuttle activity.

    • Pharmacologically activating HIF-1α or increasing succinate concentrations restores the hypoxic response and improves functional recovery post-ischemia in diabetes.
    Original languageEnglish
    Pages (from-to)485-498
    Number of pages14
    JournalJournal of the American College of Cardiology: Basic to Translational Science
    Volume3
    Issue number4
    DOIs
    Publication statusPublished - Aug 2018

    Bibliographical note

    NOTICE: this is the author’s version of a work that was accepted for publication in
    Journal of the American College of Cardiology: Basic to Translational Science
    Changes resulting from the publishing process, such as peer review, editing,
    corrections, structural formatting, and other quality control mechanisms may not
    be reflected in this document. Changes may have been made to this work since it
    was submitted for publication. A definitive version was subsequently published in
    Journal of the American College of Cardiology: Basic to Translational Science.
    © 2018, Elsevier. Licensed under the Creative Commons AttributionNonCommercial-NoDerivatives
    4.0 International
    http://creativecommons.org/licenses/by-nc-nd/4.0/

    Fingerprint

    Dive into the research topics of 'Fatty acids prevent Hypoxia-Inducible Factor 1α signalling in type 2 diabetes'. Together they form a unique fingerprint.

    Cite this