Key result
A high-sucrose and high-fat diet inducing NAFLD and NASH led to impaired glucose and lipid metabolism, deteriorated functionality in skeletal muscle, and altered myokine expression in mice.
Why the study?
The molecular characteristics and alterations in skeletal muscle during the progression of NAFLD and NASH remain unclear.
Transcriptome profiling reveals that NAFLD and NASH impair glucose and lipid metabolism in skeletal muscle, providing a molecular basis for exercise as an intervention.
May provide molecular rationale for exercise in NAFLD/NASH; leaves open translation of myokine findings from mice to humans.
Nonalcoholic fatty liver disease (NAFLD), characterized by extensive triglyceride accumulation in hepatocytes, may progress to nonalcoholic steatohepatitis (NASH) with liver fibrosis and inflammation and increase the risk of cirrhosis, cancer, and death. It has been reported that physical exercise is effective in ameliorating NAFLD and NASH, while skeletal muscle dysfunctions, including lipid deposition and weakness, are accompanied with NAFLD and NASH. However, the molecular characteristics and alterations in skeletal muscle in the progress of NAFLD and NASH remain unclear. In the present study, we provide a comprehensive analysis on the similarity and heterogeneity of quadriceps muscle in NAFLD and NASH mice models by RNA sequencing. Importantly, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analysis revealed that NAFLD and NASH led to impaired glucose and lipid metabolism and deteriorated functionality in skeletal muscle. Besides this, we identified that myokines possibly mediate the crosstalk between muscles and other metabolic organs in pathological conditions. Overall, our analysis revealed a comprehensive understanding of the molecular signature of skeletal muscles in NAFLD and NASH, thus providing a basis for physical exercise as an intervention against liver diseases.
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Guo et al. (2022) studied Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) (n=24). High-sucrose and high-fat diet vs. Chow diet was evaluated on Differentially expressed genes in quadriceps muscle. A high-sucrose and high-fat diet inducing NAFLD and NASH led to impaired glucose and lipid metabolism, deteriorated functionality in skeletal muscle, and altered myokine expression in mice.
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