title: AMP-kinase pathway is involved in tumor necrosis factor alpha-induced lipid accumulation in human hepatoma cells.
abstract: OBJECTIVE
  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-α) 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-α on lipid deposition of HepG2 cells and examine the modification of AMPK pathway.
  
  
  METHODS
  TNF-α was added in HepG2 cells and lipid accumulation was analyzed by Oil Red O 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-α in HepG2 cells to investigate its effect on TNF-α induced lipid deposition.
  
  
  RESULTS
  A significant increment of TG content in HepG2 cells was observed after TNF-α 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-α-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 ACC phosphorylation were suppressed and the inhibitory effect of metformin on HepG2 cell lipid deposition was also attenuated.
  
  
  CONCLUSIONS
  Our results suggest that TNF-α directly induces lipid accumulation in HepG2 cells, at least in part, through the inhibition of AMPK/mTOR/SREBP-1 pathway.
authors: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Qiong
authors: Q
authors: Lv
authors: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Qianna
authors: Q
authors: Zhen
authors: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Lulu
authors: L
authors: Liu
authors: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Laboratory of Lipids and Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Rufei
authors: R
authors: Gao
authors: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Shumin
authors: S
authors: Yang
authors: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Huang
authors: H
authors: Zhou
authors: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors: Richa
authors: R
authors: Goswami
authors: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: liqifu@yeah.net.
authors: Qifu
authors: Q
authors: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008113:Liver Neoplasms / Q000473:pathology*; D008687:Metformin / Q000494:pharmacology; D010766:Phosphorylation; D012265:Ribonucleotides / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D012265:Ribonucleotides; D051780:Sterol Regulatory Element Binding Protein 1; D014409:Tumor Necrosis Factor-alpha; D000620:Aminoimidazole Carboxamide; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide
keywords: AMPK; Lipid accumulation; Metformin; SREBP-1; TNF-α; mTOR