SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice
Background In non-alcoholic steatohepatitis (NASH), muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice.Methods In vivo and...
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BMJ Publishing Group
2020-12-01
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| Series: | BMJ Open Gastroenterology |
| Online Access: | https://bmjopengastro.bmj.com/content/7/1/e000381.full |
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| author | Chang-Youh Tsai Tzu-Hao Li Ying-Ying Yang Chia-Chang Huang Chih-Wei Liu Ming-Wei Lin Ming-Chih Hou Yi-Hsiang Huang Chien-Fu Hsu Yu-Lien Tsai Hung-Cheng Tsai Shiang-Fen Huang Yun-Cheng Hsieh Tzung-Yan Lee Han-Chieh Lin |
| author_facet | Chang-Youh Tsai Tzu-Hao Li Ying-Ying Yang Chia-Chang Huang Chih-Wei Liu Ming-Wei Lin Ming-Chih Hou Yi-Hsiang Huang Chien-Fu Hsu Yu-Lien Tsai Hung-Cheng Tsai Shiang-Fen Huang Yun-Cheng Hsieh Tzung-Yan Lee Han-Chieh Lin |
| author_sort | Chang-Youh Tsai |
| collection | DOAJ |
| description | Background In non-alcoholic steatohepatitis (NASH), muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice.Methods In vivo and in vitro study, we evaluate the SIRT1-dependent mechanisms and effects of resveratrol administration for 6 weeks with high-fat-methionine and choline deficient diet-induced NASH mice and palmitate-pretreated C2C12 myoblast cells.Results Resveratrol treatment improved grip strength and muscle mass of limbs, increased running distance and time on exercise wheels in NASH mice. There is a negative correlation between muscular SIRT1 activity and 3-nitrotyrosine levels of NASH and NASH-resv mice. The SIRT1-dependent effect of muscle wasting was associated with the suppression of oxidative stress, upregulation of antioxidants, inhibition of protein degradation, activation of autophagy, suppression of apoptotic activity, upregulation of lipolytic genes and the reduction of fatty infiltration in limb muscles of NASH mice. In vitro, resveratrol alleviated palmitate acid-induced oxidative stress, lipid deposition, autophagy dysfunction, apoptotic signals, and subsequently reduced fusion index and myotube formation of C2C12 cells. The beneficial effects of resveratrol were abolished by EX527.Conclusions Our study suggests that chronic resveratrol treatment is a potential strategy for amelioration of hepatic steatosis and muscle wasting in NASH mouse model. |
| format | Article |
| id | doaj-art-07e68228d27d4071a4e8e720d3df4f83 |
| institution | OA Journals |
| issn | 2054-4774 |
| language | English |
| publishDate | 2020-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Gastroenterology |
| spelling | doaj-art-07e68228d27d4071a4e8e720d3df4f832025-08-20T01:56:35ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742020-12-017110.1136/bmjgast-2020-000381SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH miceChang-Youh Tsai0Tzu-Hao Li1Ying-Ying Yang2Chia-Chang Huang3Chih-Wei Liu4Ming-Wei Lin5Ming-Chih Hou6Yi-Hsiang Huang7Chien-Fu Hsu8Yu-Lien Tsai9Hung-Cheng Tsai10Shiang-Fen Huang11Yun-Cheng Hsieh12Tzung-Yan Lee13Han-Chieh Lin145Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan, Republic of ChinaDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanDepartment of Medical Education, Taipei Veterans General Hospital, Taipei, TaiwanClinical Skill Training Center, Taipei Veterans General Hospital, Taipei, TaiwanDivision of Allergy, Immunology and Rheumatology, Taipei, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, TaiwanDivision of Gastroenterology and Hepatology, Taipei, TaiwanDepartment of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanDepartment of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanDivision of Allergy, Immunology and Rheumatology, Taipei, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei, TaiwanDepartment of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanGraduate Institute of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Linkou, TaiwanDepartment of Medicine, Taipei Veterans General Hospital, Taipei, TaiwanBackground In non-alcoholic steatohepatitis (NASH), muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice.Methods In vivo and in vitro study, we evaluate the SIRT1-dependent mechanisms and effects of resveratrol administration for 6 weeks with high-fat-methionine and choline deficient diet-induced NASH mice and palmitate-pretreated C2C12 myoblast cells.Results Resveratrol treatment improved grip strength and muscle mass of limbs, increased running distance and time on exercise wheels in NASH mice. There is a negative correlation between muscular SIRT1 activity and 3-nitrotyrosine levels of NASH and NASH-resv mice. The SIRT1-dependent effect of muscle wasting was associated with the suppression of oxidative stress, upregulation of antioxidants, inhibition of protein degradation, activation of autophagy, suppression of apoptotic activity, upregulation of lipolytic genes and the reduction of fatty infiltration in limb muscles of NASH mice. In vitro, resveratrol alleviated palmitate acid-induced oxidative stress, lipid deposition, autophagy dysfunction, apoptotic signals, and subsequently reduced fusion index and myotube formation of C2C12 cells. The beneficial effects of resveratrol were abolished by EX527.Conclusions Our study suggests that chronic resveratrol treatment is a potential strategy for amelioration of hepatic steatosis and muscle wasting in NASH mouse model.https://bmjopengastro.bmj.com/content/7/1/e000381.full |
| spellingShingle | Chang-Youh Tsai Tzu-Hao Li Ying-Ying Yang Chia-Chang Huang Chih-Wei Liu Ming-Wei Lin Ming-Chih Hou Yi-Hsiang Huang Chien-Fu Hsu Yu-Lien Tsai Hung-Cheng Tsai Shiang-Fen Huang Yun-Cheng Hsieh Tzung-Yan Lee Han-Chieh Lin SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice BMJ Open Gastroenterology |
| title | SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice |
| title_full | SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice |
| title_fullStr | SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice |
| title_full_unstemmed | SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice |
| title_short | SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice |
| title_sort | sirt1 dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in nash mice |
| url | https://bmjopengastro.bmj.com/content/7/1/e000381.full |
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