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SHR Neuro Krebs Kardio Lipid

Moustafa, T; Fickert, P; Magnes, C; Guelly, C; Thueringer, A; Frank, S; Kratky, D; Sattler, W; Reicher, H; Sinner, F; Gumhold, J; Silbert, D; Fauler, G; Höfler, G; Lass, A; Zechner, R; Trauner, M.
Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury.
Gastroenterology. 2012; 142(1):140-151
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Autor/innen der Med Uni Graz:
Fauler Günter
Fickert Peter
Frank Saša
Gülly Christian
Hoefler Gerald
Kratky Dagmar
Moustafa Tarek
Reicher Helga
Sattler Wolfgang
Silbert-Wagner Dagmar
Sinner Frank
Sommer Judith
Trauner Michael
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Abstract:
The liver controls central processes of lipid and bile acid homeostasis. We aimed to investigate whether alterations in lipid metabolism contribute to the pathogenesis of chronic cholestatic liver disease in mice. We used microarray and metabolic profiling analyses to identify alterations in systemic and hepatic lipid metabolism in mice with disruption of the gene ATP-binding cassette sub-family B member 4 (Abcb4(-/-) mice), a model of inflammation-induced cholestatic liver injury, fibrosis, and cancer. Alterations in Abcb4(-/-) mice, compared with wild-type mice, included deregulation of genes that control lipid synthesis, storage, and oxidation; decreased serum levels of cholesterol and phospholipids; and reduced hepatic long-chain fatty acyl-CoAs (LCA-CoA). Feeding Abcb4(-/-) mice the side chain-modified bile acid 24-norursodeoxycholic acid (norUDCA) reversed their liver injury and fibrosis, increased serum levels of lipids, lowered phospholipase and triglyceride hydrolase activities, and restored hepatic LCA-CoA and triglyceride levels. Additional genetic and nutritional studies indicated that lipid metabolism contributed to chronic cholestatic liver injury; crossing peroxisome proliferator-activated receptor (PPAR)-α-deficient mice with Abcb4(-/-) mice (to create double knockouts) or placing Abcb4(-/-) mice on a high-fat diet protected against liver injury, with features similar to those involved in the response to norUDCA. Placing pregnant Abcb4(-/-) mice on high-fat diets prevented liver injury in their offspring. However, fenofibrate, an activator of PPARα, aggravated liver injury in Abcb4(-/-) mice. Alterations in lipid metabolism contribute to the pathogenesis and progression of cholestatic liver disease in mice. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Bile Acids and Salts - metabolism Bile Acids and Salts - pharmacology
Cell Proliferation -
Cholestasis, Intrahepatic - drug therapy Cholestasis, Intrahepatic - genetics Cholestasis, Intrahepatic - metabolism Cholestasis, Intrahepatic - pathology
Chronic Disease -
Dietary Fats - administration & dosage Dietary Fats - metabolism
Disease Models, Animal -
Disease Progression -
Fatty Acids - metabolism
Female -
Fenofibrate - pharmacology
Gene Expression Profiling - methods
Gene Expression Regulation -
Hepatitis - drug therapy Hepatitis - genetics Hepatitis - metabolism Hepatitis - pathology
Hypolipidemic Agents - pharmacology
Lipid Metabolism - genetics
Liver - drug effects Liver - metabolism Liver - pathology
Liver Cirrhosis - drug therapy Liver Cirrhosis - genetics Liver Cirrhosis - metabolism Liver Cirrhosis - pathology
Metabolomics -
Mice -
Mice, Knockout -
Oligonucleotide Array Sequence Analysis -
P-Glycoproteins - deficiency P-Glycoproteins - genetics
PPAR gamma - deficiency PPAR gamma - genetics
Pregnancy -
Prenatal Exposure Delayed Effects -
Triglycerides - metabolism
Ursodeoxycholic Acid - analogs & derivatives Ursodeoxycholic Acid - pharmacology

Find related publications in this database (Keywords)
Cholestasis
Canalicular Phospholipid Flippase
Hepatocellular Cancer
PSC
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