Central energy metabolism remains robust in acute steatotic hepatocytes challenged by a high free fatty acid load

BMB Reports

Anne Bonin^1¹  Jens Niklas^1²  Stefanie Mangin^1³ 

[1] Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of T?bingen, Auerbachstrasse 112, D-70376 Stuttgart^2;Insilico Biotechnology AG, Meitnerstrasse 8, D-70563 Stuttgart^1;Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Johannisallee 30, D-04103 Leipzig, Germany^3

关键词: Isotope labeling;   

DOI  :  

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

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.

【 授权许可】

Unknown