High-intensity interval training (HIIT) represents a fundamental physiological stimulus for inducing mitochondrial biogenesis and increasing maximal oxygen uptake (VO₂max). Although systemic cardiovascular macro-adaptations are widely documented, the combined impact of HIIT and variations in environmental oxygen partial pressure (hypoxia and hyperoxia) on the subcellular remodeling of the myocyte requires further investigation. This longitudinal experimental study evaluates the effect of a 4x4 HIIT protocol conducted in normoxia, hypoxia, and hyperoxia on peripheral adaptations, focusing on modifications in genomic density and the intrinsic functionality of the mitochondrial reticulum. Thirty healthy subjects (18-40 years old) completed a four-week intervention structured into 12 treadmill HIIT sessions. Pre- and post-intervention assessments included incremental tests to determine VO₂max, hemodynamic measurements (femoral blood flow and cardiac output), and muscle biopsies of the vastus lateralis. High-resolution respirometry on permeabilized fibers, absolute quantification of the organellar genome (mtDNA/nDNA ratio) via qPCR, and immunohistochemical evaluations for capillary density and fiber typing were performed on the biopsy samples. It is hypothesized that training in hypoxia induces an adaptation aimed at maximizing extraction efficiency and mitochondrial thermodynamic coupling, compensating for the reduced PaO₂. Hyperoxia, acting as an ergogenic aid and removing central transport limits, would allow for sustaining higher mechanical loads; this extreme stress would trigger the AMPK/PGC-1α axis, maximizing the absolute synthesis of mtDNA. The results will clarify muscle plasticity in response to bioenergetic stress.
L'allenamento intervallato ad alta intensità (HIIT) rappresenta uno stimolo fisiologico fondamentale per l'induzione della biogenesi mitocondriale e l'incremento del massimo consumo di ossigeno (VO₂max). Sebbene i macro-adattamenti cardiovascolari sistemici siano ampiamente documentati, l'impatto combinato dell'HIIT e delle variazioni della pressione parziale di ossigeno ambientale (ipossia e iperossia) sul rimodellamento sub-cellulare del miocita richiede ulteriori indagini. Questo studio sperimentale longitudinale valuta l'effetto di un protocollo HIIT (4x4) condotto in normossia, ipossia e iperossia sugli adattamenti periferici, concentrandosi sulle modificazioni della densità genomica e sulla funzionalità intrinseca del reticolo mitocondriale. Trenta soggetti sani (18-40 anni) hanno completato un intervento di quattro settimane strutturato in 12 sessioni di HIIT su treadmill. Le valutazioni pre e post-intervento hanno incluso test incrementali per determinare il VO₂max, misurazioni emodinamiche (flusso femorale e gittata cardiaca) e prelievi bioptici del muscolo vasto laterale. Sui campioni bioptici sono state eseguite analisi di respirometria ad alta risoluzione su fibre permeabilizzate, quantificazione assoluta del genoma organulare (rapporto mtDNA/nDNA) tramite qPCR, e valutazioni immunoistochimiche per la densità capillare e la tipizzazione fibrillare. Si ipotizza che l'allenamento in ipossia induca un adattamento mirato a massimizzare l'efficienza estrattiva e l'accoppiamento termodinamico mitocondriale, compensando la ridotta PaO₂. L'iperossia, agendo da supporto ergogenico e rimuovendo i limiti centrali di trasporto, consentirebbe di sostenere carichi meccanici superiori; questo estremo stress innescherebbe l'asse AMPK/PGC-1α, massimizzando la sintesi assoluta di mtDNA. I risultati chiariranno la plasticità muscolare in risposta allo stress bioenergetico.
Modificazioni della densità e della funzionalità mitocondriale in risposta ad allenamento ad alta intensità
BARBIERI, RICCARDO
2025/2026
Abstract
High-intensity interval training (HIIT) represents a fundamental physiological stimulus for inducing mitochondrial biogenesis and increasing maximal oxygen uptake (VO₂max). Although systemic cardiovascular macro-adaptations are widely documented, the combined impact of HIIT and variations in environmental oxygen partial pressure (hypoxia and hyperoxia) on the subcellular remodeling of the myocyte requires further investigation. This longitudinal experimental study evaluates the effect of a 4x4 HIIT protocol conducted in normoxia, hypoxia, and hyperoxia on peripheral adaptations, focusing on modifications in genomic density and the intrinsic functionality of the mitochondrial reticulum. Thirty healthy subjects (18-40 years old) completed a four-week intervention structured into 12 treadmill HIIT sessions. Pre- and post-intervention assessments included incremental tests to determine VO₂max, hemodynamic measurements (femoral blood flow and cardiac output), and muscle biopsies of the vastus lateralis. High-resolution respirometry on permeabilized fibers, absolute quantification of the organellar genome (mtDNA/nDNA ratio) via qPCR, and immunohistochemical evaluations for capillary density and fiber typing were performed on the biopsy samples. It is hypothesized that training in hypoxia induces an adaptation aimed at maximizing extraction efficiency and mitochondrial thermodynamic coupling, compensating for the reduced PaO₂. Hyperoxia, acting as an ergogenic aid and removing central transport limits, would allow for sustaining higher mechanical loads; this extreme stress would trigger the AMPK/PGC-1α axis, maximizing the absolute synthesis of mtDNA. The results will clarify muscle plasticity in response to bioenergetic stress.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14251/7279