Publications

Dernière publication 01/01/2025

Oral octanoylcarnitine alleviates exercise intolerance in mouse models of long-c

ABSTRACT Long-chain fatty acid oxidation disorders (LC-FAODs) cause energy deficits in heart and skeletal muscle that is only partially corrected...

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    [title] => Oral octanoylcarnitine alleviates exercise intolerance in mouse models of long-c
    [paragraph] => Oral octanoylcarnitine alleviates exercise intolerance in mouse models of long-chain fatty acid oxidation disorders
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Authors
Keaton J. Solo, Yuxun Zhang, Sivakama S. Bharathi, Bob B. Zhang, Adam C. Richert, Alexandra V. Schmidt, Shakuntala Basu, Clinton Van’t Land, Olivia D’Annibale, Timothy C. Wood, Jerry Vockley, Eric S. Goetzman

 Lab

Journal
bioRxiv
Abstract
ABSTRACT
Long-chain fatty acid oxidation disorders (LC-FAODs) cause energy deficits in heart and skeletal muscle that is only partially corrected by current medium-chain lipid therapies such as triheptanoin. We find that heart and muscle lack medium-chain acyl-CoA synthetases, limiting the capacity for β-oxidation of medium-chain fatty acids. Instead, heart and muscle mitochondria robustly respire on medium-chain acylcarnitines. The mitochondrial matrix enzyme carnitine acetyltransferase (CrAT) efficiently converts orally delivered octanoylcarnitine (C8-carnitine) to octanoyl-CoA for energy generation. C8-carnitine exhibits twice the oral bioavailability of triheptanoin and distributes to muscle and heart. A single oral dose markedly enhances grip strength, basal locomotion, and LE8700TS endurance while attenuating lactate and creatine kinase elevations in multiple mouse models of LC-FAODs. Thus, medium-chain acylcarnitines overcome a previously unrecognized metabolic bottleneck in LC-FAOD muscle and may represent an alternative to triglyceride-based therapies for bioenergetic disorders.

Keywords/Topics
exercise
BIOSEB Instruments Used:
Grip strength test (BIO-GS4),Infrared Actimeter (LE8815)
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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