Analysis of the role of Four and a half LIM domains protein 2 (FHL2) in hepatic lipid metabolisms in non-alcoholic fatty liver disease (NAFLD)

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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Hepatic steatosis is the first step and driving force of the NAFLD-pathology. Therefore, a comprehensive understanding of the molecular mechanisms leading to the accumulation of intrahepatic lipids is critically needed to support the development of effective forms of treatments for NAFLD, which are so far missing but highly needed. FHL2 is the second member of the "four-and-a-half LIM-domain" protein-family. FHL2 is ubiquitously expressed and is involved in the regulation of various biological mechanisms in health and disease. FHL2 lacks direct DNA binding activities but interacts with numerous proteins including transcription factors, and herewith, acts as transcriptional coactivator or corepressor. Our preliminary work indicates that enhanced FHL2 expression in hepatocytes promotes liver steatosis in NAFLD. The aims of this project are to characterize the molecular mechanisms by which FHL2 affects hepatic steatosis in preclinical models and to validate the findings in clinical samples of NAFLD-patients. The overall goal is the identification of new therapeutic targets for the inhibition of the development and progression of NAFLD.