Z Gastroenterol 2015; 53 - G1
DOI: 10.1055/s-0035-1558899

Contribution of the interleukin-6-type cytokine Oncostatin M to the pathogenesis of non-alcoholic fatty liver disease

HM Hermanns 1, C Schäfer 1, S Walter 1, D Dorbath 1, C Mais 1, D Jahn 1, A Geier 1
  • 1University Hospital Würzburg (UKW), Division of Hepatology, Würzburg, Germany

Background: Oncostatin M is an IL-6 family cytokine released by activated monocytes/macrophages, neutrophils and dendritic cells in the early phase of inflammatory processes. Surprisingly, it has recently been shown to execute protective functions in high-fat diet-induced obesity and related metabolic disorders in mice. Its role in the development of non-alcoholic fatty liver disease (NAFLD) and in conjunction with hypercholesterolemia, however, has not been addressed so far.

Methods: C57Bl/6, Osmr-/-, Ldlr-/- single knockout and Ldlr-/-, Osmr-/- double knockout mice were fed a high-fat diet for 12 weeks. Weight gain was documented on a weekly basis. After 12 weeks mice were sacrificed. Liver weight was evaluated; steatosis and cellular composition were analyzed by immunohistochemistry. Serum levels of cholesterol and leptin were determined by HPLC and ELISA, respectively. Expression of liver enzymes was monitored by qPCR analyses.

Results: Confirming the published results, Osmr-/- mice gain significantly more body and liver weight in contrast to C57Bl/6 mice. However, on an Ldlr-/- background displaying hypercholesterolemia the phenotype was reversed and Ldlr-/- Osmr-/- double knockout mice gained less body and liver weight, showed lower blood glucose levels as well as serum cholesterol and leptin levels. Preliminary analyses of liver enzymes indicated a reduction in the expression of enzymes involved in fatty acid synthesis (Fasn, Elovl6, Acc, Scd1) in Ldlr-/- Osmr-/- double knockout mice.

Conclusion: Depending on the genetic background and metabolic status the IL-6-type cytokine Oncostatin M appears to exert protective or pathogenic influences on the pathogenesis of NAFLD. Further in depth characterization of the mouse models is required to understand the exact molecular mechanisms and therefore to clarify if OSM indeed might serve as a therapeutic agent for the treatment of obesity and related metabolic disorders as recently suggested.