Mo1772 Lipopolysaccharides Can Accelerate the Development of Nonalcoholic Fatty Liver Disease, Caused by the Up-Regulation of Lipogenic Gene Expressions

Background/Aim: Obesity is rapidly becoming a pandemic and is associated with increased prevalence of iron deficiency anaemia (IDA). Obese populations have higher circulating levels of leptin in contrast to low concentrations of adiponectin. Hence, it is important to evaluate the dynamic role between adiponectin and leptin in obesity-related IDA. Since leptin shares a number of common biological features with IL-6, a major factor in the development of anaemia of chronic inflammation (ACI), we speculated that leptin and its metabolic counterpart adiponectin might play a role in regulating iron metabolism in the overweight population. Methods: The human hepatoma cells HuH7 and Hep G2 were exposed to IL-6 [10-50ng/ml], leptin [0.1-10μg/ml] and adiponectin [5μg/ml] for 16 hours. mRNA expression was determined using real-time quantitative RT-PCR, protein levels were detected by western blot analysis. Both cell lines were also transfected with a hepcidin promoter-luciferase reporter gene construct to investigate transcriptional regulation of hepcidin. Results: Similar to IL-6 (***p<0.001), leptin causes a significant dose-dependent increase of hepcidin promoter activity (***p<0.001) in both cell lines, leading to elevated mRNA-levels. The activation of transcription factor STAT3 seems to play a crucial role. This was confirmed with specific STAT3-Inhibitor S3I201 [50μM] (***p<0.001). Furthermore, we were able to show for the first time that adiponectin completely abolished leptin effects on hepcidin promoter activation (***p<0.001 in HepG2, *p<0.05 in Huh7). Conclusion: Collectively, these data provide a novel insight into the molecular link between obesity and IDA and further demonstrate that adiponectin has the molecular potential to inhibit leptininduced hepcidin expression.