title: Free Fatty Acids Impair FGF21 Action in HepG2 Cells.
abstract: OBJECTIVE
  Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA).
  
  
  METHODS
  We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism.
  
  
  RESULTS
  In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism.
  
  
  CONCLUSIONS
  In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Asrih
authors.forename: Christophe
authors.initials: C
authors.lastname: Montessuit
authors.forename: Jacques
authors.initials: J
authors.lastname: Philippe
authors.forename: François R
authors.initials: FR
authors.lastname: Jornayvaz
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: C491901:FAS protein, human; D005230:Fatty Acids, Nonesterified; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase; D055372:AMP-Activated Protein Kinases; C000588423:ACACA protein, human; D000103:Acetyl-CoA Carboxylase