RESUMO
AIM: The aim of this study was to investigate the effects of rosuvastatin in a model of diet-induced obesity and non-alcoholic fatty liver disease, with attention to the activation of hepatic stellate cells (HSCs). METHOD: Male C57BL/6 mice received a control diet (C; 10% energy as lipids) or a high-fat diet (HF; 50% energy as lipids) for 12 weeks, followed by 7 weeks of treatment. Group CR received control diet + rosuvastatin; group HFR received high-fat diet + rosuvastatin. RESULTS: The HF group showed higher insulin, total cholesterol, triacylglycerol, and leptin levels than the C group, all of which were significantly diminished by rosuvastatin in the HFR group. The HF group had greater steatosis and activated HSCs than the C group, whereas rosuvastatin diminished the steatosis (less 21%, P < 0.001) and significantly inhibited the activation of the HSCs in the HFR group compared to the HF group. The sterol regulatory element-binding protein-1 and the peroxisome proliferator-activated receptor (PPAR)-γ protein expressions were increased in HF animals and reduced after treatment in the HFR group. By contrast, low PPAR-α and carnitine palmitoyltransferase-1 expressions were found in the HF group, and were restored by rosuvastatin treatment in the HFR group. CONCLUSION: Rosuvastatin mitigated hepatic steatosis by modulating PPAR balance, favoring PPAR-α over PPAR-γ downstream effects. The effects were accompanied by a diminishing of insulin resistance, the anti-inflammatory adipokine profile, and HSC activation, avoiding non-alcoholic fatty liver disease progression and non-alcoholic steatohepatitis onset in this model.