Z Gastroenterol 2012; 50 - P1_55
DOI: 10.1055/s-0031-1295787

MMP–9 activity is increased by adiponectin in primary human hepatocytes but negatively correlates with serum adiponectin in a rodent model of non-alcoholic steatohepatitis

R Walter 1, J Wanninger 1, S Bauer 1, K Eisinger 1, A Schäffler 1, C Dorn 2, TS Weiss 3, C Hellerbrand 2, C Buechler 1
  • 1Klinik und Poliklinik für Innere Medizin I, Universität Regensburg, Regensburg
  • 2Department of Internal Medicine I, University Hospital Regensburg, Regensburg
  • 3Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Regensburg, Regensburg

Objective: Adiponectin protects from inflammation and fibrosis in metabolic liver disease. In the present study we analyzed whether this adipokine may directly affect the activity of matrix metalloproteinases (MMPs), central regulators of fibrinolysis, in hepatocytes. Methods: Primary human hepatocytes and liver of patients with and without liver steatosis were used. Human liver tissue was obtained according to the guidelines of the charitable state-controlled foundation Human Tissue & Cell Research (HTCR) with the patient's informed consent. To induce NASH mice were fed a Paigen diet for 12 weeks or a methionine-choline deficient diet for 6 weeks. Results: Global gene expression analysis indicated upregulation of MMP–9 and tissue inhibitor of metalloproteinases–1 (TIMP–1) expression in primary human hepatocytes (PHH) in response to stimulation with adiponectin, and these results were confirmed by real-time RT-PCR. Furthermore, gelatin zymography revealed that MMP–9 activity was significantly induced in supernatants of adiponectin stimulated PHHs. In a murine model of hepatic steatosis and in human steatotic liver samples hepatic MMP–9 activity was not significantly altered. However, in two different murine models of non-alcoholic stetaohepatitis (NASH) MMP–9 activity was significantly elevated compared to chow fed control mice. Of note, MMP–9 activity did not or even negatively, respectively, correlate with adiponection serum levels in these models. Conclusion: In NASH hepatic inflammation and fibrosis but not hepatic steatosis induce liver MMP–9 activity, and this induction seems to be related to the anti-inflammatory activity of adiponectin rather than its effect on hepatocellular MMP–9 expression.