科研之友
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摘要
Aim: It is well known that lipid accumulation and inflammation are two important steps in pathogenesis and progress of nonalcoholic fatty liver disease (NAFLD). However, fewer studies have explored the direct relationship between lipid accumulation and inflammation in early NAFLD. Tumor necrosis factor alpha (TNF-alpha) is one of the classical inflammatory cytokines. AMP-activated protein kinase (AMPK) is known as a critical regulator of energy homeostasis in metabolic processes. This study aims to investigate the role of TNF-alpha on lipid deposition of HepG2 cells and examine the modification of AMPK pathway. Main methods: TNF-alpha was added in HepG2 cells and lipid accumulation was analyzed by Oil Red 0 staining and quantitative test of triglyceride (TG). The expressions of phosphorylated AMPK and its pathway (including mTOR and SREBP-1) were determined. Furthermore, an AMPK agonist (metformin or AICAR) or antagonist (compound C) was co-administrated with TNF-alpha in HepG2 cells to investigate its effect on TNF-alpha induced lipid deposition. Key findings: A significant increment of TG content in HepG2 cells was observed after TNF-alpha treatment. Meanwhile, substantially suppressed AMPK and ACC phosphorylation, enhanced mTOR and p70S6K phosphorylation, and increased protein expression of FAS and SREBP-1 were found. Co-treatment with metformin or AICAR decreased the TNF-alpha-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions. On the contrary, while co-incubated with compound C,AMPK and All phosphorylation were suppressed and the inhibitory effect of metformin on HepG2 cell lipid deposition was also attenuated. Significance: Our results suggest that TNF-alpha directly induces lipid accumulation in HepG2 cells, at least in part, through the inhibition of AMPK/mTOR/SREBP-1 pathway.
- 出版日期2015-6-15
- 单位重庆医科大学
