Apparent hepatic fibrosis and the accumulation of hepatic lipid droplets developed in the IVA-PLA 2-conditional knockout mice on a high-fat diet for nine weeks to a similar degree as in control mice. We examined the potential utility of IVA-PLA 2 of HSCs as a therapeutic target for hepatic fibrosis in NASH under dietary modification using collagen-producing cell-specific IVA-PLA 2-conditional knockout mice fed a high-fat diet and then returned to a normal one. The activation of cultured HSCs has been shown to be attenuated by pharmacological inhibition of group IVA phospholipase A 2 (IVA-PLA 2), an enzyme initiating the generation of lipid proinflammatory mediators. Currently, no approved pharmacotherapy is available to treat hepatic fibrosis, even under dietary intervention. Hepatic fibrosis, a primary feature of non-alcoholic steatohepatitis (NASH), develops with inflammation and subsequent activation of hepatic stellate cells (HSCs), the main extracellular matrix-producing cells.
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