Rosuvastatina, doença hepática gordurosa não alcoólica e ativação das células estreladas hepáticas em camundongos

Abstract

The current obesity epidemic has called attention to the most common hepatic obesity feature, the nonalcoholic fatty liver disease (NAFLD). There is no drug for treating NAFLD, though statins are greatly prescribed for obese patients. This work aimed to investigate the effects of Rosuvastatin in a model of diet-induced obesity and NAFLD, focusing on hepatic markers of lipogenesis and beta-oxidation and activation of HSCs in mice. Methods: Male C57BL/6 mice received a standard chow diet (SC, 10% energy as lipids) or high-fat diet (HF, 50% energy as lipids) for 12 weeks, followed by 7 weeks of treatment, forming the groups: SC, SCR (SC + Rosuvastatin), HF and HFR (HF + Rosuvastatin). Biochemical analyzes and molecular techniques were applied to address the plasma and molecular outcomes. Results: HF group had higher insulin, total cholesterol, triacylglycerol and leptin levels than SC group, all of which were significantly diminished by rosuvastatina in HFR group. HF group showed greater steatosis than SC group and activated hepatic stellate cells (HSCs), whereas rosuvastatin elicited a 21% decrease in steatosis and greatly inhibited the HSCs activation in HFR group. In agreement to histological findings, SREBP-1 and PPARgamma expression were increased in HF animals and reduced after the treatment in HFR group. By contrast, low PPARalpha and CPT-1 expression were found in HF animals, being restored by the treatment in HFR group. Conclusion: Rosuvastatin has the advantage of significantly inhibit the activation of HSCs in diet-induced obesity, by affecting PPAR balance to counter lipotoxicity. Rosuvastatin should be thought to treat hepatic steatosis.