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Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes
Hypoxia-inducible factor (HIF)-1α is essential following a myocardial infarction (MI), and diabetic patients have poorer prognosis post-MI. Could HIF-1α activation be abnormal in the diabetic heart, and could metabolism be causing this? Diabetic hearts had decreased HIF-1α protein following ischemia...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115650/ https://www.ncbi.nlm.nih.gov/pubmed/30175272 http://dx.doi.org/10.1016/j.jacbts.2018.04.005 |
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author | Dodd, Michael S. Sousa Fialho, Maria da Luz Montes Aparicio, Claudia N. Kerr, Matthew Timm, Kerstin N. Griffin, Julian L. Luiken, Joost J.F.P. Glatz, Jan F.C. Tyler, Damian J. Heather, Lisa C. |
author_facet | Dodd, Michael S. Sousa Fialho, Maria da Luz Montes Aparicio, Claudia N. Kerr, Matthew Timm, Kerstin N. Griffin, Julian L. Luiken, Joost J.F.P. Glatz, Jan F.C. Tyler, Damian J. Heather, Lisa C. |
author_sort | Dodd, Michael S. |
collection | PubMed |
description | Hypoxia-inducible factor (HIF)-1α is essential following a myocardial infarction (MI), and diabetic patients have poorer prognosis post-MI. Could HIF-1α activation be abnormal in the diabetic heart, and could metabolism be causing this? Diabetic hearts had decreased HIF-1α protein following ischemia, and insulin-resistant cardiomyocytes had decreased HIF-1α-mediated signaling and adaptation to hypoxia. This was due to elevated fatty acid (FA) metabolism preventing HIF-1α protein stabilization. FAs exerted their effect by decreasing succinate concentrations, a HIF-1α activator that inhibits the regulatory HIF hydroxylase enzymes. In vivo and in vitro pharmacological HIF hydroxylase inhibition restored HIF-1α accumulation and improved post-ischemic functional recovery in diabetes. |
format | Online Article Text |
id | pubmed-6115650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-61156502018-08-31 Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes Dodd, Michael S. Sousa Fialho, Maria da Luz Montes Aparicio, Claudia N. Kerr, Matthew Timm, Kerstin N. Griffin, Julian L. Luiken, Joost J.F.P. Glatz, Jan F.C. Tyler, Damian J. Heather, Lisa C. JACC Basic Transl Sci PRECLINICAL RESEARCH Hypoxia-inducible factor (HIF)-1α is essential following a myocardial infarction (MI), and diabetic patients have poorer prognosis post-MI. Could HIF-1α activation be abnormal in the diabetic heart, and could metabolism be causing this? Diabetic hearts had decreased HIF-1α protein following ischemia, and insulin-resistant cardiomyocytes had decreased HIF-1α-mediated signaling and adaptation to hypoxia. This was due to elevated fatty acid (FA) metabolism preventing HIF-1α protein stabilization. FAs exerted their effect by decreasing succinate concentrations, a HIF-1α activator that inhibits the regulatory HIF hydroxylase enzymes. In vivo and in vitro pharmacological HIF hydroxylase inhibition restored HIF-1α accumulation and improved post-ischemic functional recovery in diabetes. Elsevier 2018-08-28 /pmc/articles/PMC6115650/ /pubmed/30175272 http://dx.doi.org/10.1016/j.jacbts.2018.04.005 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | PRECLINICAL RESEARCH Dodd, Michael S. Sousa Fialho, Maria da Luz Montes Aparicio, Claudia N. Kerr, Matthew Timm, Kerstin N. Griffin, Julian L. Luiken, Joost J.F.P. Glatz, Jan F.C. Tyler, Damian J. Heather, Lisa C. Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes |
title | Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes |
title_full | Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes |
title_fullStr | Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes |
title_full_unstemmed | Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes |
title_short | Fatty Acids Prevent Hypoxia-Inducible Factor-1α Signaling Through Decreased Succinate in Diabetes |
title_sort | fatty acids prevent hypoxia-inducible factor-1α signaling through decreased succinate in diabetes |
topic | PRECLINICAL RESEARCH |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115650/ https://www.ncbi.nlm.nih.gov/pubmed/30175272 http://dx.doi.org/10.1016/j.jacbts.2018.04.005 |
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