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Given that L-carnitine uptake into skeletal muscle occurs slowly and is influenced by insulin availability and training status, chronic exposure to elevated plasma LC levels may eventually reduce the responsiveness of transport mechanisms or alter carnitine homeostasis

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While chronic hypoxia drives long-term metabolic reprogramming and stable epigenetic alterations ( 2.2 Hypoxia-inducible factors Hypoxia-inducible factors (HIFs) are central regulators of the cellular response to low oxygen tension and play a pivotal role in mediating the adaptive changes observed in hypoxic tumors ( Figure 4 ) ( Figure 5 ), HIF-1 is continuously synthesized but rapidly degraded through the oxygen-dependent activity of prolyl hydroxylase domain (PHD) enzymes, which hydroxylate specific proline residues (Pro-564 and Pro-402) within the oxygen-dependent degradation domain (ODD) of the HIF-1 subunit

Carnitine and acylcarnitines: Pharmacokinetic, pharmacological and clinical aspects