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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Quiroga, AD; Li, L; Trötzmüller, M; Nelson, R; Proctor, SD; Köfeler, H; Lehner, R.
Deficiency of carboxylesterase 1/esterase-x results in obesity, hepatic steatosis, and hyperlipidemia.
Hepatology. 2012; 56(6):2188-2198
Doi: 10.1002/hep.25961
[OPEN ACCESS]
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Köfeler Harald
- Trötzmüller Martin
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- Abstract:
- 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 omega-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. (HEPATOLOGY 2012;56:2188-2198)
- Find related publications in this database (using NLM MeSH Indexing)
- Analysis of Variance -
- Animals -
- Blood Glucose - metabolism
- Carboxylic Ester Hydrolases - deficiency
- Cholesterol - metabolism
- Docosahexaenoic Acids - metabolism
- Energy Metabolism -
- Fasting -
- Fatty Acids, Unsaturated - administration & dosage
- Fatty Liver - enzymology
- Female -
- Fish Oils - administration & dosage
- Gene Expression -
- Hepatocytes - metabolism
- Hyperlipidemias - enzymology
- Insulin - blood
- Lipoproteins, VLDL - secretion
- Mice -
- Mice, Knockout -
- Obesity - enzymology
- Phenotype -
- Phospholipids - metabolism
- Sterol Regulatory Element Binding Protein 1 - genetics
- Triglycerides - metabolism