Es-x/Ces1 prevents triacylglycerol accumulation in McArdle-RH7777 hepatocytes.
Mouse esterase-x/carboxylesterase 1 (Es-x/Ces1) is a close homolog of triacylglycerol hydrolase/carboxylesterase 3 (TGH/Ces3). Es-x possesses a conserved esterase/lipase active site motif, suggesting that like TGH it could play a role in hepatic triacylglycerol (TG) metabolism. McArdle-RH7777 cells stably transfected with Es-x cDNA accumulated significantly less TG and had increased production of acid-soluble metabolites (an indicator of beta-oxidation) during incubations with 0.4mM oleic acid when compared to empty vector or TGH cDNA transfected cells. Reduction of cellular TG persisted in the presence of esterase/lipase inhibitor E600 indicating that Es-x-mediated TG lowering can be largely explained by reduced partitioning of exogenous fatty acids to TG and increased redirection to beta-oxidation, rather than by increased TG turnover. Glycerol supplementation increased TG synthesis in both control and Es-x expressing cells to similar extent suggesting that Es-x expression did not reduce flux of metabolic intermediates through the glycerol-3-phosphate pathway. While Es-x expression reduced cellular TG levels, secretion of TG and apolipoprotein B remained unchanged when compared to control cells. Overall, these results suggest that Es-x limits hepatic TG accumulation by promoting beta-oxidation.
Ko
Kerry W S
KW
Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Erickson
Bruce
B
Lehner
Richard
R
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000378:metabolism; D005990:Glycerol / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D019301:Oleic Acid / Q000378:metabolism; D063065:Organophosphonates / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010261:Paraoxon / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism*
D001055:Apolipoproteins B; D005227:Fatty Acids; D063065:Organophosphonates; D011994:Recombinant Proteins; D014280:Triglycerides; D019301:Oleic Acid; D002265:Carboxylic Ester Hydrolases; C545375:carboxylesterase 1, mouse; D005990:Glycerol; D010261:Paraoxon