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

• Published in: Molecular nutrition & food research Vol. 69; no. 16; pp. e70091 - n/a
• Main Authors: Berraaouan, Ali, Legssyer, Abdelkhaleq, Bnouham, Mohamed
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.08.2025
• Subjects: Animals; Atrophy; Chemical synthesis; Diabetes mellitus; Fatty acids; Fatty Acids - pharmacology; Geriatrics; Humans; Molecular modelling; muscle atrophy; Muscle Proteins - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Muscular Atrophy - metabolism; Musculoskeletal system; nutrition; Older people; Pharmacology; Protein turnover; proteostasis; Proteostasis - drug effects; Skeletal muscle; nutrition; protein turnover; muscle atrophy; fatty acids; proteostasis; skeletal muscle
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.70091

ABSTRACT 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. Skeletal muscle atrophy is a morbid systemic condition. It could be the result of aging, muscle disuse, or a disease such as diabetes and cancer. In atrophying muscle, protein turnover is unbalanced with an amplified pro‐atrophy signaling resulting in a high‐rate protein degradation and a low‐rate protein synthesis. Fatty acids improve muscle condition by fine‐tuning a panoply of molecular processes to reestablish muscle protein homeostasis and reinforce muscle resilience against pro‐atrophy conditions. Fatty acids promote protein synthesis and lower their degradation in atrophying muscle which contributes to a balanced protein metabolism in muscle fiber. Embracing the health effects of fatty acids unveils a promising strategy to fortify muscles and uphold overall physical well‐being.2