Knockdown of Sirt1 Gene in Mice Results in Lipid Accumulation in the Liver Mediated via PGC-1α-Induced Mitochondrial Dysfunction and Oxidative Stress.

Abstract

The study demonstrated the crucial role of Sirt1 gene in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) related to the influence of Sirt1 on oxidative stress and glycolipid metabolism. The 16-week-old genetically diabetic db/db mice were characterized with downregulated expression of Sirt1 in the liver accompanied by hepatomegaly and a larger size of fat vacuoles in hepatocytes. In db/m mice, silencing Sirt1 gene induced hepatic steatosis and significantly increased serum AST. Additionally, the levels of triglycerides in blood and liver of these mice were elevated. However, all pathological changes in the liver of Sirt1-knockdown db/m mice were less pronounced than in 16-week-old db/db mice. Further experiments showed that oxidative stress and PGC-1α-mediated mitochondrial dysfunction are implicated in pathological changes of lipid metabolism in T2DM-induced NAFLD provoked by Sirt1 silencing. This study showed that down-regulation of Sirt1 expression plays the key role in pathological processes developed during T2DM-induced abnormalities of lipid metabolism in the liver. Thus, up-regulation of Sirt1 expression seems to be a promising strategy in early prevention of T2DM-induced NAFLD.

• Authors: H Yang, Y Liu, Y Wang, S Xu, D Su
• Journal: Bulletin of experimental biology and medicine (Bull Exp Biol Med) Vol. 172 Issue 2 Pg. 180-186 (Dec 2021) ISSN: 1573-8221 [Electronic] United States
• PMID: 34853966 (Publication Type: Journal Article)
• Copyright: © 2021. Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Animals
• Diabetes Mellitus, Experimental (complications, genetics, metabolism, pathology)
• Gene Knockdown Techniques
• Lipid Metabolism (genetics)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mitochondria (physiology)
• Non-alcoholic Fatty Liver Disease (genetics, metabolism, pathology)
• Oxidative Stress (genetics)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (physiology)
• Signal Transduction (genetics)
• Sirtuin 1 (genetics)