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Comprehensive Transcriptome Profiling of NAFLD- and NASH-Induced Skeletal Muscle Dysfunction
Mingwei Guo1, Liping Xiang2, Jing Yao1
1Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Frontiers in Endocrinology
|March 10, 2022
Summary
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) impair skeletal muscle by disrupting glucose and lipid metabolism. Understanding these molecular changes in muscle is key for developing exercise interventions for liver disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Exercise Physiology
Background:
- Nonalcoholic fatty liver disease (NAFLD) involves liver triglyceride accumulation and can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis.
- Skeletal muscle dysfunction, including lipid deposition and weakness, is associated with NAFLD and NASH, but molecular alterations are not fully understood.
Purpose of the Study:
- To comprehensively analyze molecular similarities and differences in skeletal muscle during NAFLD and NASH progression.
- To elucidate the impact of NAFLD and NASH on skeletal muscle's metabolic function and identify potential therapeutic targets.
Main Methods:
- Utilized RNA sequencing to compare quadriceps muscle molecular profiles in NAFLD and NASH mouse models.
- Performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to interpret functional changes.
Main Results:
- NAFLD and NASH significantly impair glucose and lipid metabolism in skeletal muscle.
- Skeletal muscle functionality deteriorates in both NAFLD and NASH conditions.
- Identified myokines as potential mediators of communication between skeletal muscle and other organs in these diseases.
Conclusions:
- Skeletal muscle exhibits distinct molecular signatures in NAFLD and NASH.
- These findings provide a molecular basis for understanding skeletal muscle's role in liver disease progression.
- Supports the potential of physical exercise as an intervention strategy for NAFLD and NASH.
