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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Central energy metabolism remains robust in acute steatotic hepatocytes challenged by a high free fatty acid load

  • Niklas, Jens (Insilico Biotechnology AG) ;
  • Bonin, Anne (Insilico Biotechnology AG) ;
  • Mangin, Stefanie (Insilico Biotechnology AG) ;
  • Bucher, Joachim (Insilico Biotechnology AG) ;
  • Kopacz, Stephanie (Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tubingen) ;
  • Matz-Soja, Madlen (Institute of Biochemistry, Faculty of Medicine, University of Leipzig) ;
  • Thiel, Carlo (Institute of Biochemistry, Faculty of Medicine, University of Leipzig) ;
  • Gebhardt, Rolf (Institute of Biochemistry, Faculty of Medicine, University of Leipzig) ;
  • Hofmann, Ute (Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tubingen) ;
  • Mauch, Klaus (Insilico Biotechnology AG)
  • Received : 2012.03.21
  • Accepted : 2012.04.17
  • Published : 2012.07.31
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Abstract

Overnutrition is one of the major causes of non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by an accumulation of lipids (triglycerides) in hepatocytes and is often accompanied by high plasma levels of free fatty acids (FFA). In this study, we compared the energy metabolism in acute steatotic and non-steatotic primary mouse hepatocytes. Acute steatosis was induced by pre-incubation with high concentrations of oleate and palmitate. Labeling experiments were conducted using [$U-^{13}C_5$,$U-^{15}N_2$] glutamine. Metabolite concentrations and mass isotopomer distributions of intracellular metabolites were measured and applied for metabolic flux estimation using transient $^{13}C$ metabolic flux analysis. FFAs were efficiently taken up and almost completely incorporated into triglycerides (TAGs). In spite of high FFA uptake rates and the high synthesis rate of TAGs, central energy metabolism was not significantly changed in acute steatotic cells. Fatty acid ${\beta}$-oxidation does not significantly contribute to the detoxification of FFAs under the applied conditions.

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References

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