Astaxanthin alleviates oxidative stress and skeletal muscle damage by promoting mitochondrial biogenesis

Introduction This study aimed to investigate the damaging effects of a high-fat diet (HFD) on mitochondria and skeletal muscle and to evaluate the protective role of astaxanthin (Asta), with a focus on mitochondrial biogenesis, oxidative stress, and inflammation under metabolic stress. Methods HFD-fed mice and palmitate acid (PA)-stimulated C2C12 cells were treated with Asta. Skeletal muscle function, pathology, mitochondrial ultrastructure, inflammatory responses, and oxidative stress levels were assessed using behavioral tests, histology, quantitative reverse transcription-polymerase chain reaction, western blotting, transmission electron microscopy, and biochemical assays. Results Asta did not alter body weight or serum lipid levels in HFD-fed mice but markedly alleviated skeletal muscle damage and improved function. In both in vivo and in vitro models, Asta suppressed inflammatory gene expression, enhanced mitochondrial biogenesis-related proteins, reduced lipid accumulation and mitochondrial damage, increased antioxidant enzyme activity, and promoted ATP production. Furthermore, Asta inhibited mitochondrial fission and lipid peroxidation in PA-stimulated C2C12 cells. Discussion Asta mitigates oxidative stress, lipid accumulation, and inflammation in skeletal muscle cells by promoting mitochondrial biogenesis, thereby preserving muscle structure and function. These findings highlight Asta’s potential as a therapeutic agent for skeletal muscle protection in metabolic stress conditions.