A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice
Sild-Met-Leu treatment increases PPAR alpha and delta in mouse hepatocyte-macrophage coculture. Mouse hepatocytes and macrophages, grown individually or in coculture, were treated with sildenafil (1 nM), metformin (0.1 mM), and leucine (0.5 mM) as indicated for 24 hours after induction with free fatty acids (FFA) and LPS. Nontreated cells with induction with FFA and LPS (FFA + LPS) or without (control) were included for comparison. ((a) and (b)) Gene expression of PPAR alpha and delta in hepatocyte-macrophage coculture. Data are represented as mean ± SEM of fold change of control ( to 8). ((c) to (f)) Protein expression of PPAR alpha and delta in RAW 264.7 macrophages and in in AML 12 hepatocytes. Quantitative data are presented as mean ± SEM ( to 5), and representative blots are shown.