Wanninger, Josef and Neumeier, Markus and Hellerbrand, Claus and Schacherer, Doris and Bauer, Sabrina and Weiss, Thomas S. and Huber, Hanna and Schaeffler, Andreas and Aslanidis, Charalampos and Schoelmerich, Juergen and Buechler, Christa (2011) Lipid accumulation impairs adiponectin-mediated induction of activin A by increasing TGFbeta in primary human hepatocytes. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1811 (10). pp. 626-633. ISSN 1388-1981,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled 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 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 May 2020 08:29 |
| Last Modified: | 29 May 2020 08:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20136 |
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