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Redox state as a master regulator of liver function
Author(s) -
Nocito Laura,
Yoo Elsia J,
Corkey Barbara E
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.565.5
Subject(s) - extracellular , glutathione , intracellular , redox , ketone bodies , reactive oxygen species , hepatocyte , biochemistry , mitochondrion , endogeny , respiration , chemistry , metabolism , cellular respiration , oxygen , oxidative phosphorylation , biology , enzyme , anatomy , organic chemistry , in vitro
Objective To determine if redox, as a regulator of metabolic and mitochondrial responses, controls the fate of fuels and liver function by generating reactive oxygen species (ROS). Methods Primary hepatocytes were treated with extracellular redox couples: cysteine/cystine (Cys/CySS), reduced/oxidized glutathione (GSH/GSSG), βhydroxybutyrate/acetoacetate (βOHB/Acoc) and lactate/pyruvate (L/P). ROS generation was measured using H2DCFDA. Endogenous glucose production and circulating redox metabolites were measured from cell incubation media using fluorescent methods. Oxygen consumption was measured using the XF24 extracellular analyzer. Results Redox couple induced oxidized conditions increased intracellular ROS generation. Endogenous glucose production, mitochondrial respiration, and ketone bodies and L/P secretions were also analyzed. Both endogenous glucose production and mitochondrial respiration decreased under oxidized conditions, whereas the ratios of ketone bodies (βOHB/Acoc) and L/P secretions increased. Conclusions We show that oxidized extracellular conditions induce ROS in primary hepatocytes. The extracellular oxidized milieu determined by βOHB/Acoc causes a decrease in the maximal respiratory capacity induced by the uncoupler FCCP. These effects are associated with a decrease in hepatocyte gluconeogenic capacity.