Liver-specific expression of carboxylesterase 1g/esterase-x reduces hepatic steatosis, counteracts dyslipidemia and improves insulin signaling

Wesam Bahitham; Russell Watts; Randal Nelson; Jihong Lian; Richard Lehner

doi:10.1016/j.bbalip.2016.03.009

Liver-specific expression of carboxylesterase 1g/esterase-x reduces hepatic steatosis, counteracts dyslipidemia and improves insulin signaling

Biochim Biophys Acta. 2016 May;1861(5):482-90. doi: 10.1016/j.bbalip.2016.03.009. Epub 2016 Mar 11.

Authors

Wesam Bahitham¹, Russell Watts², Randal Nelson², Jihong Lian², Richard Lehner³

Affiliations

¹ 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.
² 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.
³ 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.

PMID: 26976727
DOI: 10.1016/j.bbalip.2016.03.009

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.

Keywords: Carboxylesterase; Insulin resistance; Lipase; Steatosis; Triglyceride; VLDL.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Glucose / metabolism
Carboxylic Ester Hydrolases / deficiency
Carboxylic Ester Hydrolases / genetics
Carboxylic Ester Hydrolases / metabolism*
Disease Models, Animal
Fatty Liver / blood
Fatty Liver / enzymology
Fatty Liver / genetics
Fatty Liver / prevention & control*
Female
Gene Expression Regulation
Gene Transfer Techniques
Genetic Predisposition to Disease
Genetic Therapy*
Hyperlipidemias / blood
Hyperlipidemias / enzymology
Hyperlipidemias / genetics
Hyperlipidemias / prevention & control*
Insulin / blood*
Insulin Resistance*
Lipid Droplets / metabolism
Lipid Metabolism* / genetics
Lipoproteins, VLDL / blood
Liver / enzymology*
Mice, Knockout
Phenotype
Signal Transduction
Time Factors
Triglycerides / blood

Substances

Blood Glucose
Insulin
Lipoproteins, VLDL
Triglycerides
very low density lipoprotein triglyceride
Carboxylic Ester Hydrolases
carboxylesterase 1, mouse

Grants and funding

MOP-106518/Canadian Institutes of Health Research/Canada