Alterations in Autophagy and Mammalian Target of Rapamycin (mTOR) Pathways Mediate Sarcopenia in Patients with Cirrhosis
| Autor: | Virinder Kumar Bansal, Shyam S. Chauhan, Samagra Agarwal, Anoop Saraya, Mehar Chand Sharma, Vikas Kumar, Abhinav Anand, Namrata Singh, Kanav Kaushal, Deepak Gunjan, Sanchit Sharma, Kumble Seetharama Madhusudhan, Srikanth Gopi, Aruna Nambirajan, Srikant Mohta |
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| Rok vydání: | 2022 |
| Předmět: |
Muscle tissue
medicine.medical_specialty Cirrhosis Population H&E stain 03 medical and health sciences 0302 clinical medicine Internal medicine medicine education education.field_of_study Muscle biopsy Hepatology medicine.diagnostic_test business.industry Skeletal muscle medicine.disease Muscle atrophy medicine.anatomical_structure Endocrinology 030220 oncology & carcinogenesis Sarcopenia Original Article 030211 gastroenterology & hepatology medicine.symptom business |
| Zdroj: | J Clin Exp Hepatol |
| ISSN: | 0973-6883 |
| DOI: | 10.1016/j.jceh.2021.05.004 |
| Popis: | Background and aims The pathophysiology of sarcopenia in cirrhosis is poorly understood. We aimed to evaluate the histological alterations in the muscle tissue of patients with cirrhosis and sarcopenia, and identify the regulators of muscle homeostasis. Methods Computed tomography images at third lumbar vertebral level were used to assess skeletal muscle index (SMI) in 180 patients. Sarcopenia was diagnosed based on the SMI cut-offs from a population of similar ethnicity. Muscle biopsy was obtained from the vastus lateralis in 10 sarcopenic patients with cirrhosis, and the external oblique in five controls (voluntary kidney donors during nephrectomy). Histological changes were assessed by hematoxylin and eosin staining and immunohistochemistry for phospho-FOXO3, phospho-AKT, phospho-mTOR, and apoptosis markers (annexin V and caspase 3). The messenger ribonucleic acid (mRNA) expressions for MSTN, FoxO3, markers of ubiquitin-proteasome pathway (FBXO32, TRIM63), and markers of autophagy (Beclin-1 and LC3) were also quantified. Results The prevalence of sarcopenia was 14.4%. Muscle histology in sarcopenics showed atrophic angulated fibers (p = 0.002) compared to controls. Immunohistochemistry showed a significant loss of expression of phospho-mTOR (p = 0.026) and an unaltered phospho-AKT (p = 0.089) in sarcopenic patients. There were no differences in the immunostaining for annexin-V, caspase-3, and phospho-FoxO3 between the two groups. The mRNA expressions of MSTN and Beclin-1 were higher in sarcopenics (p = 0.04 and p = 0.04, respectively). The two groups did not differ in the mRNA levels for TRIM63, FBXO32, and LC3. Conclusions Significant muscle atrophy, increase in autophagy, MSTN gene expression, and an impaired mTOR signaling were seen in patients with sarcopenia and cirrhosis. |
| Databáze: | OpenAIRE |
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