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KMID : 0624620120450070396
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BMB Reports
2012 Volume.45 No. 7 p.396 ~ p.401
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Central energy metabolism remains robust in acute steatotic hepatocytes challenged by a high free fatty acid load
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Niklas Jens
Bonin Anne
Mangin Stefanie
Bucher Joachim
Kopacz Stephanie
Matz-Soja Madlen
Thiel Carlo
Gebhardt Rolf
Hofmann Ute
Mauch Klaus
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Abstract
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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.
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KEYWORD
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Isotope labeling, Liver, Metabolic flux, Non-alcoholic fatty liver disease NAFLD, Steatosis, Transient 13C MFA
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