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 journalArticle

10 Citations (Scopus)
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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/

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