Academic Journal
Elucidation of SIRT-1/PGC-1α-associated mitochondrial dysfunction and autophagy in nonalcoholic fatty liver disease
| العنوان: | Elucidation of SIRT-1/PGC-1α-associated mitochondrial dysfunction and autophagy in nonalcoholic fatty liver disease |
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| المؤلفون: | Jiang, Yan, Chen, Duankai, Gong, Qiming, Xu, Qunqing, Pan, Dong, Lu, Feiyan, Tang, Qianli |
| المساهمون: | Guangxi Clinical Medical Research Center of hepatobiliary Diseases |
| المصدر: | Lipids in Health and Disease ; volume 20, issue 1 ; ISSN 1476-511X |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2021 |
| الوصف: | Background Nonalcoholic fatty liver disease (NAFLD) can lead to chronic liver diseases associated with mitochondrial damages. However, the exact mechanisms involved in the etiology of the disease are not clear. Methods To gain new insights, the changes affecting sirtuin 1 (SIRT-1) during liver fat accumulation was investigated in a NAFLD mouse model. In addition, the in vitro research investigated the regulation operated by SIRT-1 on mitochondrial structures, biogenesis, functions, and autophagy. Results In mice NAFLD, high-fat-diet (HFD) increased body weight gain, upregulated serum total cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, blood glucose, insulin levels, and liver malondialdehyde, and decreased liver superoxide dismutase activity. In liver, the levels of SIRT-1 and peroxisome proliferator-activated receptor-gamma coactivator -1α (PGC-1α) decreased. The expression of peroxisome proliferator-activated receptor-α and Beclin-1 proteins was also reduced, while p62/SQSTM1 expression increased. These results demonstrated SIRT-1 impairment in mouse NAFLD. In a well-established NAFLD cell model, exposure of the HepG2 hepatocyte cell line to oleic acid (OA) for 48 h caused viability reduction, apoptosis, lipid accumulation, and reactive oxygen species production. Disturbance of SIRT-1 expression affected mitochondria. Pre-treatment with Tenovin-6, a SIRT-1 inhibitor, aggravated the effect of OA on hepG2, while this effect was reversed by CAY10602, a SIRT-1 activator. Further investigation demonstrated that SIRT-1 activity was involved in mitochondrial biogenesis through PGC-1α and participated to the balance of autophagy regulatory proteins. Conclusion In conclusion, in high-fat conditions, SIRT-1 regulates multiple cellular properties by influencing on mitochondrial physiology and lipid autophagy via the PGC-1α pathway. The SIRT-1/PGC-1α pathway could be targeted to develop new NAFLD therapeutic strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s12944-021-01461-5 |
| DOI: | 10.1186/s12944-021-01461-5.pdf |
| DOI: | 10.1186/s12944-021-01461-5/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s12944-021-01461-5 https://link.springer.com/content/pdf/10.1186/s12944-021-01461-5.pdf https://link.springer.com/article/10.1186/s12944-021-01461-5/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.E795D875 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12944-021-01461-5 |
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