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

• Published in: Biochimica et biophysica acta Vol. 1861; no. 5; pp. 482 - 490
• Main Authors: Bahitham, Wesam, Watts, Russell, Nelson, Randal, Lian, Jihong, Lehner, Richard
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-05-2016
• Subjects: Animals; Blood Glucose - metabolism; Carboxylesterase; 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; Lipase; Lipid Droplets - metabolism; Lipid Metabolism - genetics; Lipoproteins, VLDL - blood; Liver - enzymology; Mice, Knockout; Phenotype; Signal Transduction; Steatosis; Time Factors; Triglyceride; Triglycerides - blood; VLDL; PBS; AST; CE; NAFLD; Ad; DG; GTT; ITT; ALT; Ces1g/Es-x; McA; NASH; Carboxylesterase; Lipase; Triglyceride; ER; Steatosis; TG; VLDL; Insulin resistance; FA; PL; ApoB; FC
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2016.03.009

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.
•Mice deficient in Ces1g/Es-x develop metabolic syndrome phenotype.•Hepatic Ces1g/Es-x regulates liver lipid content.•Hepatic Ces1g/Es-x decreases VLDL secretion and lipogenesis.•Hepatic Ces1g/Es-x improves insulin signaling.