Fatty Acids and Proteostasis in Skeletal Muscle Atrophy: Mechanistic Insights From In Vitro and Preclinical Findings

Skeletal muscle atrophy is a threatening condition related to aging and other pathologies such as diabetes and cancer. Thus, the development of groundbreaking therapeutic strategies is mandatory for better management of skeletal muscle atrophy in the elderly and diseased individuals. Nutritional interventions have gained recognition as fundamental strategies for attenuating or preventing the advancement of skeletal muscle atrophy, with particular attention focused on fatty acids as potential therapeutic agents. This review synthesizes contemporary knowledge regarding the molecular mechanisms through which isolated fatty acids (distinct from complex oils or mixtures) may exert beneficial effects against muscle atrophy focusing on proteostasis. The discussion begins with an overview of protein turnover regulation in skeletal muscle tissue, subsequently providing a comprehensive examination of the anti-atrophic properties of fatty acids at the molecular level. While preclinical studies utilizing laboratory models have demonstrated the therapeutic potential of fatty acids in modulating muscle atrophy pathways, translation to clinical applications requires further investigation to establish mechanistic understanding and reproducible efficacy in human subjects.