SIRT3 reduces lipid accumulation via AMPK activation in human hepatic cells
| Autor: | Guo Quan Fan, Shu Dong Xiao, Tong Shi |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adenosine monophosphate
SIRT3 AMP-Activated Protein Kinases chemistry.chemical_compound AMP-activated protein kinase Lipid droplet Sirtuin 3 Medicine Humans Phosphorylation Protein kinase A biology business.industry Gastroenterology AMPK Hep G2 Cells Lipid Metabolism Cell biology Biochemistry chemistry biology.protein Hepatocytes NAD+ kinase business Deacetylase activity Acetyl-CoA Carboxylase |
| Zdroj: | Journal of digestive diseases. 11(1) |
| ISSN: | 1751-2980 |
| Popis: | OBJECTIVE: Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylase localized on mitochondria and regulates the adaptive thermogenesis in brown adipocytes. This study aims to investigate the role of SIRT3 in hepatic lipid accumulation, and whether the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) is required. METHODS: A retroviral system was used for overexpressing of SIRT3 in HepG2 cells, whereas a lentivirus-mediated vector encoding SIRT3 small interfering RNA (siRNA) was used to infect these cells for knocking down endogenous SIRT3 expression. The cells were treated with oleate to induce lipid accumulation and Nile red staining was used to assess the number of lipid droplets in HepG2 cells. The AMPK signaling pathway was facilitated with the administrating of isoproterenol and an immunoblot analysis was performed to assess the phosphorylation of AMPK and acetyl coenzyme A carboxylase (ACC). Compound C was adopted to inhibit AMPK activity. RESULTS: The number of lipid droplets in HepG2 cells overexpressing SIRT3 was significantly lower than that in the control cells (P < 0.05). SIRT3-infected cells exhibited significantly more phosphorylation of AMPK and ACC (P < 0.05), which was reversed by the treatment of compound C, an inhibitor of AMPK. Knocking down SIRT3 downregulated phosphorylation of AMPK and ACC by 60–80% (P < 0.05) and promoted lipid accumulation. The activation of AMPK by SIRT3 was dependent on SIRT3 deacetylase activity. CONCLUSION: SIRT3 reduces lipid accumulation via AMPK activation in human hepatic cells. |
| Databáze: | OpenAIRE |
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