title: Rosuvastatin limits the activation of hepatic stellate cells in diet-induced obese mice.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thatiany de Souza
authors.initials: TS
authors.lastname: Marinho
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Kawasaki
authors.affiliation: Faculty of Medicine, Linköping University, Linköping, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bryntesson
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Souza-Mello
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Barbosa-da-Silva
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcia B
authors.initials: MB
authors.lastname: Aguila
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
keywords: NAFLD; beta-oxidation; hepatic stellate cells; lipogenesis; statin; stereology