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Fig. 7 | BMC Medical Genomics

Fig. 7

From: Genomics of lipid-laden human hepatocyte cultures enables drug target screening for the treatment of non-alcoholic fatty liver disease

Fig. 7

Western blotting and immunofluorescence imaging of PLIN2 and a schematic overview of LD associated gene regulations in lipid-laden hepatocytes. Cultures of primary human hepatocyte and hepatoma cell lines were treated with a mixture of 0.5 mM PA/OA or the combined lipid and TNFα treatment. a Western blotting of Plin2 with GAPDH as loading control.*** p < 0.01. b Immunofluorescence of DMSO vehicle and lipid treated hepatocytes highlighting PLIN2 localization around the monolayer of LDs. The lipids were stained with MDP dye and the scale bar is 7.5 μm. c Overview of mechanistically linked and LD associated genes in an in-vitro model of fatty liver disease. Depicted is a summary of NAFLD responsive genes in steatotic hepatocyte cultures. Fatty acid uptake occurs either by diffusion or lipid transporters. Continuous supply of lipids leads to an imbalance in glycolysis and gluconeogenesis that in turn affects β-oxidation of fatty acids. The excess lipids are stored in the form of lipid droplets. Simultaneously, genes responsible for LD growth are up-regulated and support LD expansion. The hepatocytes also respond to external stimulus such as TNFα signals by up-regulating mitogen activated protein kinases as well as other inflammatory signals such as interleukins and suppressors of cytokine signaling. Overall, cellular homeostasis is disturbed leading to enhanced lipid synthesis and altered metabolic signaling and eventually augments lipotoxicity. Figure 7c had been created by the authors

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