Publications

Latest 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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An easy way to objectively quantify the muscular strength of mice and rats, and to assess the effect of drugs, toxins, muscular (i.e. myopathy) and neurodegenerative diseases on muscular degeneration. It is widely used in conjunction with the ROTAROD motor coordination test: a normally coordinated rodent will show a decreased latency to fall off the rotating rod if its muscular strength is low. The Grip Strength Test is a must for your research on activity, motor control & coordination, and is particularly well suited for studies on Parkinson's & Huntington's disease.
New features GS4 - 2023: Color display with permanent backlight screen for easier reading, reset by footswitch, Improved battery time, Larger data memory of 500 values, Animal counter, USB port (charging/data transfer)

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