title: Liver-specific expression of carboxylesterase 1g/esterase-x reduces hepatic steatosis, counteracts dyslipidemia and improves insulin signaling.
abstract: Ces1g/Es-x deficiency in mice results in weight gain, insulin resistance, fatty liver and hyperlipidemia through upregulation of de novo lipogenesis and oversecretion of triacylglycerol (TG)-rich lipoproteins. Here, we show that restoration of Ces1g/Es-x expression only in the liver significantly reduced hepatic TG concentration accompanied by decreased size of lipid droplets, reduced secretion of very low-density lipoproteins and improved insulin-mediated signal transduction in the liver. Collectively, these results demonstrate that hepatic Ces1g/Es-x plays a critical role in limiting hepatic steatosis, very low-density lipoprotein assembly and in augmenting insulin sensitivity.
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; King Abdullah International Medical Research Center (KAIMRC), Jeddah, Saudi Arabia.
authors.forename: Wesam
authors.initials: W
authors.lastname: Bahitham
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors.forename: Russell
authors.initials: R
authors.lastname: Watts
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors.forename: Randal
authors.initials: R
authors.lastname: Nelson
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors.forename: Jihong
authors.initials: J
authors.lastname: Lian
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Electronic address: richard.lehner@ualberta.ca.
authors.forename: Richard
authors.initials: R
authors.lastname: Lehner
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D006949:Hyperlipidemias / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D066292:Lipid Droplets / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000201:enzymology*; D018345:Mice, Knockout; D010641:Phenotype; D015398:Signal Transduction; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D002265:Carboxylic Ester Hydrolases; C545375:carboxylesterase 1, mouse
keywords: Carboxylesterase; Insulin resistance; Lipase; Steatosis; Triglyceride; VLDL