Deficiency of carboxylesterase 1/esterase-x results in obesity, hepatic steatosis, and hyperlipidemia.

Abstract

UNLABELLED:

Increased lipogenesis, together with hyperlipidemia and increased fat deposition, contribute to obesity and associated metabolic disorders including nonalcoholic fatty liver disease. Here we show that carboxylesterase 1/esterase-x (Ces1/Es-x) plays a regulatory role in hepatic fat metabolism in the mouse. We demonstrate that Ces1/Es-x knockout mice present with increased hepatic lipogenesis and with oversecretion of apolipoprotein B (apoB)-containing lipoproteins (hepatic very-low density lipoproteins), which leads to hyperlipidemia and increased fat deposition in peripheral tissues. Consequently, Ces1/Es-x knockout mice develop obesity, fatty liver, hyperinsulinemia, and insulin insensitivity on chow diet without change in food intake and present with decreased energy expenditure. Ces1/Es-x deficiency prevents the release of polyunsaturated fatty acids from triacylglycerol stores, leading to an up-regulation of sterol regulatory element binding protein 1c-mediated lipogenesis, which can be reversed with dietary ω-3 fatty acids.

CONCLUSION:

These studies support a role for Ces1/Es-x in the partitioning of regulatory fatty acids and concomitant control of hepatic lipid biosynthesis, secretion, and deposition.

• Authors: Ariel D Quiroga, Lena Li, Martin Trötzmüller, Randy Nelson, Spencer D Proctor, Harald Köfeler, Richard Lehner
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 56 Issue 6 Pg. 2188-98 (Dec 2012) ISSN: 1527-3350 [Electronic] United States
• PMID: 22806626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Association for the Study of Liver Diseases.

Chemical References

• Blood Glucose
• Fatty Acids, Unsaturated
• Fish Oils
• Insulin
• Lipoproteins, VLDL
• Phospholipids
• Sterol Regulatory Element Binding Protein 1
• Triglycerides
• Docosahexaenoic Acids
• Cholesterol
• Carboxylic Ester Hydrolases
• carboxylesterase 1, mouse

Topics

• Analysis of Variance
• Animals
• Blood Glucose (metabolism)
• Carboxylic Ester Hydrolases (deficiency, genetics, metabolism)
• Cholesterol (metabolism)
• Docosahexaenoic Acids (metabolism)
• Energy Metabolism
• Fasting
• Fatty Acids, Unsaturated (administration & dosage, metabolism)
• Fatty Liver (enzymology, genetics)
• Female
• Fish Oils (administration & dosage)
• Gene Expression
• Hepatocytes (metabolism)
• Hyperlipidemias (enzymology, genetics)
• Insulin (blood)
• Lipoproteins, VLDL (metabolism)
• Mice
• Mice, Knockout
• Non-alcoholic Fatty Liver Disease
• Obesity (enzymology, genetics)
• Phenotype
• Phospholipids (metabolism)
• Sterol Regulatory Element Binding Protein 1 (genetics, metabolism)
• Triglycerides (metabolism)