Item type: | Article | ||||||
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Open Access Type: | No Open Access | ||||||
Journal or Publication Title: | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | ||||||
Publisher: | ELSEVIER SCIENCE BV | ||||||
Place of Publication: | AMSTERDAM | ||||||
Volume: | 1811 | ||||||
Number of Issue or Book Chapter: | 10 | ||||||
Page Range: | pp. 626-633 | ||||||
Date: | 8 November 2010 | ||||||
Institutions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin | ||||||
Projects (Historical): | DFG BU 1141/3-2, DFG BU 1141/3-3 | ||||||
Identification Number: |
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Keywords: | NONALCOHOLIC FATTY LIVER; NF-KAPPA-B; HEPATIC STEATOSIS; INSULIN-RESISTANCE; IN-VITRO; PLASMA ADIPONECTIN; STELLATE CELLS; DISEASE; RECEPTORS; ACID; Lipid accumulation; Hepatocyte; Activin A; Adiponectin | ||||||
Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||
Status: | Published | ||||||
Refereed: | Yes, this version has been refereed | ||||||
Created at the University of Regensburg: | Yes | ||||||
Item ID: | 58919 |
Abstract
Fatty liver is commonly detected in obesity and has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of liver diseases. Transforming growth factor beta (TGF beta) and activin A. both members of the TGF beta superfamiliy, are central regulators in liver fibrosis and regeneration, and the effect of hepatocyte lipid accumulation on the release of these ...

Abstract
Fatty liver is commonly detected in obesity and has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of liver diseases. Transforming growth factor beta (TGF beta) and activin A. both members of the TGF beta superfamiliy, are central regulators in liver fibrosis and regeneration, and the effect of hepatocyte lipid accumulation on the release of these proteins was studied. Primary human hepatocytes (PHH) were incubated with palmitic acid or oleic acid to increase lipid storage. Whereas activin A and its natural inhibitor follistatin were not affected, TGF beta was 2-fold increased. The hepatoprotective adipokine adiponectin dose-dependently induced activin A while lowering follistatin but did not alter TGF beta. Activin A was markedly reduced in hepatocyte cell lines compared to PHH and was not induced upon adiponectin incubation demonstrating significant differences of primary and transformed cells. In free fatty acid (FFA)-incubated PHH adiponectin-mediated induction of activin A was impaired. Inhibition of TGF beta receptors ALK4/5 and blockage of SMAD3 phosphorylation rescued activin A synthesis in FFA and in TGF beta incubated cells suggesting that FFA inhibit adiponectin activity by inducing TGF beta. To evaluate whether serum levels of activin A and its antagonist are altered in patients with hepatic steatosis, both proteins were measured in the serum of patients with sonographically diagnosed fatty liver and age- and BMI-matched controls. Systemic adiponectin was significantly reduced in patients with fatty liver but activin A and follistatin were not altered. In summary the current data demonstrate that lipid accumulation in hepatocytes induces TGF beta which impairs adiponectin bioactivity, and thereby may contribute to liver injury. (C) 2010 Published by Elsevier B.V.
Metadata last modified: 21 Aug 2024 10:17