Mitochondrial fatty acid beta-oxidation
a possible therapeutic target for skeletal muscle lipotoxicity in peripheral artery disease myopathy
DOI:
https://doi.org/10.17179/excli2024-7004Keywords:
peripheral artery disease (PAD), mitochondria, age, ectopic lipids, fatty acid beta oxidation (FAO), acetyl coenzyme A carboxylase 2 (ACC2)Abstract
Peripheral artery disease (PAD) is an atherosclerotic disease impacting over 200 million individuals and the prevalence increases with age. PAD occurs when plaque builds up within the peripheral arteries, leading to reduced blood flow and oxygen supply to the outer extremities. Individuals who experience PAD suffer from ischemia, which is typically accompanied by significant damage to skeletal muscles. Additionally, this tissue damage affects mitochondria, causing them to become dysregulated and dysfunctional, resulting in decreased metabolic rates. As there is no known cure for PAD, researchers are exploring potential therapeutic targets by examining coexisting cardiovascular conditions and metabolic risk factors, such as the aging process. Among these comorbidities, type-two diabetes mellitus and obesity are particularly common in PAD cases. These conditions, along with aging itself, are associated with an elevated accumulation of ectopic lipids within skeletal muscles, similar to what is observed in PAD. Researchers have attempted to reduce excess lipid accumulation by increasing the rate of fatty acid beta oxidation. Manipulating acetyl coenzyme A carboxylase 2, a key regulatory protein of fatty acid beta oxidation, has been the primary focus of such research. When acetyl coenzyme A carboxylase 2 is inhibited, it interrupts the conversion of acetyl-CoA into malonyl-CoA, resulting in an increase in the rate of fatty acid beta oxidation. By utilizing samples from PAD patients and applying the pharmacological strategies developed for acetyl coenzyme A carboxylase 2 in diabetes and obesity to PAD, a potential new therapeutic avenue may emerge, offering hope for improved quality of life for individuals suffering from PAD.
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Copyright (c) 2024 Cassandra E. Bradley, Emma Fletcher, Trevor Wilkinson, Andrew Ring, Lucas Cardona Ferrer, Dimitrios Miserlis, Pal Pacher, Panagiotis Koutakis
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