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Metabolites 2016, 6(1), 1;

Metabolic Flux Distribution during Defatting of Steatotic Human Hepatoma (HepG2) Cells

Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA
Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital and the Shriners Hospitals for Children, Boston, MA 02114, USA
Authors to whom correspondence should be addressed.
Academic Editor: Peter Meikle
Received: 2 December 2015 / Revised: 23 December 2015 / Accepted: 29 December 2015 / Published: 4 January 2016
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Methods that rapidly decrease fat in steatotic hepatocytes may be helpful to recover severely fatty livers for transplantation. Defatting kinetics are highly dependent upon the extracellular medium composition; however, the pathways involved are poorly understood. Steatosis was induced in human hepatoma cells (HepG2) by exposure to high levels of free fatty acids, followed by defatting using plain medium containing no fatty acids, or medium supplemented with a cocktail of defatting agents previously described before. We measured the levels of 28 extracellular metabolites and intracellular triglyceride, and fed the data into a steady-state mass balance model to estimate strictly intracellular fluxes. We found that during defatting, triglyceride content decreased, while beta-oxidation, the tricarboxylic acid cycle, and the urea cycle increased. These fluxes were augmented by defatting agents, and even more so by hyperoxic conditions. In all defatting conditions, the rate of extracellular glucose uptake/release was very small compared to the internal supply from glycogenolysis, and glycolysis remained highly active. Thus, in steatotic HepG2 cells, glycolysis and fatty acid oxidation may co-exist. Together, these pathways generate reducing equivalents that are supplied to mitochondrial oxidative phosphorylation. View Full-Text
Keywords: fatty liver; steatosis; defatting; beta-oxidation; mass balances; liver transplantation; hepatocytes fatty liver; steatosis; defatting; beta-oxidation; mass balances; liver transplantation; hepatocytes

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Yarmush, G.; Santos, L.; Yarmush, J.; Koundinyan, S.; Saleem, M.; Nativ, N.I.; Schloss, R.S.; Yarmush, M.L.; Maguire, T.J.; Berthiaume, F. Metabolic Flux Distribution during Defatting of Steatotic Human Hepatoma (HepG2) Cells. Metabolites 2016, 6, 1.

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