Research Article Details
| Article ID: | A50791 |
| PMID: | 35265044 |
| Source: | Front Endocrinol (Lausanne) |
| Title: | Comprehensive Transcriptome Profiling of NAFLD- and NASH-Induced Skeletal Muscle Dysfunction. |
| Abstract: | 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. |
| DOI: | 10.3389/fendo.2022.851520 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |