ABSTRACT Background Cisplatin (CIS) is a widely used broad‐spectrum anticancer agent, but its clinical application is often limited by severe adverse effects, including skeletal muscle atrophy, which compromises patients' quality of life and treatment efficacy. Although β‐aminoisobutyric acid (BAIBA) has demonstrated protective effects across multiple organs, its potential to mitigate cisplatin‐induced skeletal muscle atrophy remains unclear. This study aimed to evaluate the protective effects of BAIBA against cisplatin‐induced skeletal muscle atrophy. Methods Thirty‐six 8‐week‐old C57BL/6 mice were randomly assigned to four groups: control ( n = 6), BAIBA ( n = 10), CIS ( n = 10), and BAIBA+ CIS ( n = 10). Mice in the BAIBA and BAIBA+ CIS groups received oral administration of BAIBA (100 mg/kg/d) for 14 days. During the final 4 days, the CIS and BAIBA+ CIS groups received intraperitoneal cisplatin (3 mg/kg/d). Muscle wet weight and cross‐sectional area of muscle fibers were measured to assess the degree of atrophy. Reference‐based transcriptome sequencing and quantitative real‐time PCR were employed to analyze the changes in gene expression. Western blotting was performed to quantify the relative protein abundance of muscular atrophy‐related proteins. Results BAIBA effectively counteracts cisplatin‐induced muscle wasting by preserving total skeletal muscle mass and maintaining myofiber structural integrity, although it had no significant effect on grip strength in this model. Mechanistically, BAIBA suppressed E3 ubiquitin ligase expression in cisplatin‐treated mice. In addition, this intervention downregulated genes related to cisplatin‐induced apoptosis and amino acid metabolism. Moreover, it significantly modulated the expression of autophagy‐related and ferroptosis‐related genes. Conclusions These results show that BAIBA ameliorates cisplatin‐induced skeletal muscle atrophy in mice by regulating genes involved in E3 ubiquitin ligase signaling, apoptosis, amino acid metabolism, autophagy, and ferroptosis.
Wang et al. (Sun,) studied this question.