Characterization of the signaling pathway triggered by Maresin-2 in hepatocytes

Abstract

Omega-3 lipids are able of affect hepatic function, specially by reducing de novo lipogenesis and hepatic glucose production. Our preliminary data suggest that the desaturasde enzyme stearoyl desaturase-1 (Scd1) is a potential target for these anti-lipogenic lipids. The increase in Scd1 activity leads to the hepatic production of mounsaturated fatty acids (MUFAs), which in turns is required for the increase in triacylglycerol (TAG) production and accumulation. Maresin-2 is a lipid metabolite that is produced in brown adipose tissue (BAT) and released into the circulation in cold conditions. We believe that Maresin-2 may serve as a lipid messenger connecting adipose tissue and liver under negative energy balance conditions in order to suppress hepatic lipogenesis and gluconeogenesis. In this study we will test the hypothesis that Maresin-2 suppress either hepatic lipogenesis or gluconeogenesis and will understand the mechanism of action of such lipid in hepatocytes. For this purpose, we will perform in vitro studies in cultured hepatocytes in order to evaluate the ability of Maresin-2 to: suppress the gene and protein expression of major lipogenic and gluconeogenic genes, to increase fatty acid oxidation, and to reduce lipid and glucose production in the cultured hepatocytes. Yet, we aim to delete the main potential molecular targets, e.g. Scd1, in order to understand the biochemical pathways required for Maresin actions in hepatocytes.