Fabio Sarto, Christopher S Fry, Marco V Narici, Lee Rubin, Feodor D Price
{"title":"Potential of synergist ablation to study mechanisms of skeletal muscle hypertrophy in rodent disease models.","authors":"Fabio Sarto, Christopher S Fry, Marco V Narici, Lee Rubin, Feodor D Price","doi":"10.1152/ajpcell.00076.2025","DOIUrl":null,"url":null,"abstract":"<p><p>Synergist ablation (SA) is a well-established model of mechanical overload-induced hypertrophy in rodents, commonly used to infer skeletal muscle adaptation to resistance training in humans. Given the critical role of skeletal muscle atrophy in chronic conditions such as neuromuscular, metabolic, and cardiopulmonary disorders, SA represents a promising preclinical tool to study muscle hypertrophy mechanisms in pathological states. However, while extensively characterized in healthy animals, the potential applications of SA in disease models remain largely overlooked. This Mini-Review summarizes existing studies employing SA in rodent disease models, highlighting the diverse hypertrophic responses observed across conditions, including Duchenne muscular dystrophy, obesity, diabetes, cancer cachexia, and chronic kidney disease. Although hypertrophy gains are generally attenuated in diseased animals compared to healthy controls, SA-induced overload provides valuable insights into disease-specific regulatory mechanisms, including alterations in intracellular signaling, fiber-type transitions, and disease phenotype. We also discuss the strengths and limitations of SA as a preclinical model for resistance training in disease contexts and propose its broader adoption for mechanistic investigations into skeletal muscle plasticity under pathological conditions.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Cell physiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1152/ajpcell.00076.2025","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Synergist ablation (SA) is a well-established model of mechanical overload-induced hypertrophy in rodents, commonly used to infer skeletal muscle adaptation to resistance training in humans. Given the critical role of skeletal muscle atrophy in chronic conditions such as neuromuscular, metabolic, and cardiopulmonary disorders, SA represents a promising preclinical tool to study muscle hypertrophy mechanisms in pathological states. However, while extensively characterized in healthy animals, the potential applications of SA in disease models remain largely overlooked. This Mini-Review summarizes existing studies employing SA in rodent disease models, highlighting the diverse hypertrophic responses observed across conditions, including Duchenne muscular dystrophy, obesity, diabetes, cancer cachexia, and chronic kidney disease. Although hypertrophy gains are generally attenuated in diseased animals compared to healthy controls, SA-induced overload provides valuable insights into disease-specific regulatory mechanisms, including alterations in intracellular signaling, fiber-type transitions, and disease phenotype. We also discuss the strengths and limitations of SA as a preclinical model for resistance training in disease contexts and propose its broader adoption for mechanistic investigations into skeletal muscle plasticity under pathological conditions.
期刊介绍:
The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.