BMB Rep. 2012; 45(7): 396-401  
Central energy metabolism remains robust in acute steatotic hepatocytes challenged by a high free fatty acid load
Jens Niklas1,*, Anne Bonin1, Stefanie Mangin1, Joachim Bucher1, Stephanie Kopacz2, Madlen Matz-Soja3, Carlo Thiel3, Rolf Gebhardt3, Ute Hofmann2 & Klaus Mauch1
1Insilico Biotechnology AG, Meitnerstrasse 8, D-70563 Stuttgart, 2Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of T?bingen, Auerbachstrasse 112, D-70376 Stuttgart, 3Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany
Correspondence to: Tel: +49-711-460594-24; Fax: +49-711-460594-10; E-mail: jens.niklas@insilico-biotechnology.com
Received: March 21, 2012; Revised: April 12, 2012; Accepted: April 17, 2012; Published online: July 31, 2012.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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 13C 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 β-oxidation does not significantly contribute to the detoxification of FFAs under the applied conditions.
Keywords: Isotope labeling, Liver, Metabolic flux, Non-alcoholic fatty liver disease NAFLD, Steatosis, Transient 13C MFA

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