Article
Genistein shows beneficial influence on metabolic and signal pathways in an in vitro hepatic steatosis model
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Authors
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Georg Damm
- Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Allgemein-, Visceral- und Transplantationschirurgie, Berlin
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Anne Krüger
- Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Allgemein-, Visceral- und Transplantationschirurgie, Berlin
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Sebastian Lünse
- Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Allgemein-, Visceral- und Transplantationschirurgie, Berlin
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Andreas Nüssler
- Berufsgenossenschaftliche Unfallklinik Tübingen, Klinik für Unfall- und Wiederherstellungschirurgie, Tübingen
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Matthias Glanemann
- Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Klinik für Allgemein-, Visceral- und Transplantationschirurgie, Berlin
| Published: | April 23, 2012 |
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Outline
Text
Introduction: Steatosis as a first step in obesity has become pivotal in surgical interventions and organ transplantation. Postoperatively, this results in decreased liver regeneration, hepatic failure and at worst death of the patient. Therefore, there is need for fast clearance of liver fat from a surgical point of view. Epidemiologic studies suggest that Genistein (GEN) has a beneficial influence on lipid metabolism. Our aim was to establish an in vitro steatosis model in order to investigate the effects of GEN on hepatic lipid metabolism.
Material and methods: Primary human hepatocytes (PHH) were isolated from human liver resectates using a two step collagenase perfusion technique. Steatosis was induced by treatment with free fatty acids (FFA). GEN was then applied for 24h in concentrations up to 100µM. Lipid content was measured by Oil-Red-O and SRB staining. Using western blot analysis, cytosolic and nuclear protein of SREBP1c and PPARalpha as well as phosphorylation levels of the insulin targets Akt, ERK1/2, GSK3 and FOXO1 were measured.
Results: The steatotic cells showed a significant increase in lipid content compared to control PHH. In steatotic PHH, insulin signalling was impaired, shown by decreased phosphorylation of Akt, ERK1/2, FOXO1 and GSK3.Additional GEN treatment leads to increased phosphorylation of Akt, ERK1/2 and GSK3 in control but not in steatotic PHH. Nuclear protein content of PPARalpha was elevated and cleaved SREBP1c was decreased by GEN, both in a concentration dependent manner.
Conclusion: Our data suggest that the in vitro steatosis model represents the in vivo situation of hepatic steatosis very well. GEN leads to increased insulin sensitivity in control but not in steatotic PHH. Elevated nuclear PPARalpha and decreased SREBP1c levels suggest a beneficial influence on lipid metabolism. Therefore a potential use of GEN as a drug for therapeutical reduction of hepatic fatty degeneration is conceivable.
This study was supported by the Virtual Liver Network, BMBF 0315741.
