A new study, published in the Journal of Clinical and Translational Hepatology, has shed light on the close and potentially harmful relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia, a condition marked by loss of muscle mass and strength. While the two disorders often occur together, it has remained unclear whether one directly causes the other or how they biologically interact.
To explore this, researchers used Mendelian randomization, a genetic method that helps assess cause-and-effect relationships. Their analysis showed that reduced muscle mass and poor muscle function increase the risk of developing MASLD. This adds to previous evidence suggesting that MASLD itself can also contribute to sarcopenia, pointing toward a two-way causal relationship.
The team also conducted experiments in multiple mouse models, including diet-induced MASLD, genetic MASLD models, a steatotic model, and a drug-induced muscle atrophy model. Mice with MASLD showed clear signs of muscle loss, reduced strength, and abnormal fat accumulation within skeletal muscle. On the other hand, mice with muscle atrophy developed worse liver damage, including increased fat buildup, inflammation, and fibrosis.
Further analysis using multi-tissue transcriptomic profiling of liver and muscle tissues revealed important molecular changes. Sarcopenia disrupted liver metabolic balance by increasing fatty acid uptake and reducing oxidative phosphorylation. Meanwhile, MASLD worsened muscle health by promoting inflammation and metabolic dysfunction.
Importantly, the researchers identified two key signaling molecules involved in liver–muscle communication: C-C motif chemokine ligand 2 (CCL2), a muscle-derived factor that promotes MASLD, and adrenomedullin (ADM), a liver-derived hormone that contributes to muscle loss.
Overall, the findings highlight that MASLD and sarcopenia are interconnected conditions that may fuel each other. Targeting this liver–muscle signaling axis could offer new therapeutic strategies, though further studies are needed to clarify disease progression and underlying pathways.
REFERENCE: Song, Y., et al. (2026). Bidirectional Regulation between Metabolic Dysfunction-associated Steatotic Liver Disease and Sarcopenia via Liver-muscle Crosstalk. Journal of Clinical and Translational Hepatology. DOI: 10.14218/jcth.2025.00538. https://www.xiahepublishing.com/2310-8819/JCTH-2025-00538
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