Experimental evidence and clinical implications of Warburg effect in the skeletal muscle of Fabry disease
© 2023 The Authors..
Skeletal muscle (SM) pain and fatigue are common in Fabry disease (FD). Here, we undertook the investigation of the energetic mechanisms related to FD-SM phenotype. A reduced tolerance to aerobic activity and lactate accumulation occurred in FD-mice and patients. Accordingly, in murine FD-SM we detected an increase in fast/glycolytic fibers, mirrored by glycolysis upregulation. In FD-patients, we confirmed a high glycolytic rate and the underutilization of lipids as fuel. In the quest for a tentative mechanism, we found HIF-1 upregulated in FD-mice and patients. This finding goes with miR-17 upregulation that is responsible for metabolic remodeling and HIF-1 accumulation. Accordingly, miR-17 antagomir inhibited HIF-1 accumulation, reverting the metabolic-remodeling in FD-cells. Our findings unveil a Warburg effect in FD, an anaerobic-glycolytic switch under normoxia induced by miR-17-mediated HIF-1 upregulation. Exercise-intolerance, blood-lactate increase, and the underlying miR-17/HIF-1 pathway may become useful therapeutic targets and diagnostic/monitoring tools in FD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
iScience - 26(2023), 3 vom: 17. März, Seite 106074 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gambardella, Jessica [VerfasserIn] |
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| Links: |
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| Themen: |
Cell biology |
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| Anmerkungen: |
Date Revised 08.03.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2023.106074 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM353856185 |
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| 245 | 1 | 0 | |a Experimental evidence and clinical implications of Warburg effect in the skeletal muscle of Fabry disease |
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| 520 | |a © 2023 The Authors. | ||
| 520 | |a Skeletal muscle (SM) pain and fatigue are common in Fabry disease (FD). Here, we undertook the investigation of the energetic mechanisms related to FD-SM phenotype. A reduced tolerance to aerobic activity and lactate accumulation occurred in FD-mice and patients. Accordingly, in murine FD-SM we detected an increase in fast/glycolytic fibers, mirrored by glycolysis upregulation. In FD-patients, we confirmed a high glycolytic rate and the underutilization of lipids as fuel. In the quest for a tentative mechanism, we found HIF-1 upregulated in FD-mice and patients. This finding goes with miR-17 upregulation that is responsible for metabolic remodeling and HIF-1 accumulation. Accordingly, miR-17 antagomir inhibited HIF-1 accumulation, reverting the metabolic-remodeling in FD-cells. Our findings unveil a Warburg effect in FD, an anaerobic-glycolytic switch under normoxia induced by miR-17-mediated HIF-1 upregulation. Exercise-intolerance, blood-lactate increase, and the underlying miR-17/HIF-1 pathway may become useful therapeutic targets and diagnostic/monitoring tools in FD | ||
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| 700 | 1 | |a Fiordelisi, Antonella |e verfasserin |4 aut | |
| 700 | 1 | |a Cerasuolo, Federica Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Buonaiuto, Antonietta |e verfasserin |4 aut | |
| 700 | 1 | |a Avvisato, Roberta |e verfasserin |4 aut | |
| 700 | 1 | |a Viti, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Sommella, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Merciai, Fabrizio |e verfasserin |4 aut | |
| 700 | 1 | |a Salviati, Emanuela |e verfasserin |4 aut | |
| 700 | 1 | |a Campiglia, Pietro |e verfasserin |4 aut | |
| 700 | 1 | |a D'Argenio, Valeria |e verfasserin |4 aut | |
| 700 | 1 | |a Parisi, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Bianco, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Spinelli, Letizia |e verfasserin |4 aut | |
| 700 | 1 | |a Di Vaia, Eugenio |e verfasserin |4 aut | |
| 700 | 1 | |a Cuocolo, Alberto |e verfasserin |4 aut | |
| 700 | 1 | |a Pisani, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Riccio, Eleonora |e verfasserin |4 aut | |
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| 700 | 1 | |a Sorriento, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Iaccarino, Guido |e verfasserin |4 aut | |
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