Factors involved in rosuvastatin induction of insulin sensitization in rats fed a high fat diet

Nutr Metab Cardiovasc Dis. 2013 Nov;23(11):1107-14. doi: 10.1016/j.numecd.2012.11.009. Epub 2013 Feb 20.


Background and aim: To investigate whether rosuvastatin can improve insulin sensitivity in overweight rats having a high fat diet (HFD). The potential mechanisms involved in this action were evaluated, including SIRT-1, other factors involved in glucose metabolism and stress signaling pathways.

Methods and results: Male Wistar rats (n = 30) were divided into three groups: (i) rats fed a standard diet (3.5% fat); (ii) rats fed a HFD (33.5% fat); and (iii) rats fed a HFD and treated with rosuvastatin (15 mg/kg/day). Evolution: 7 weeks. HFD rats showed increased body, epididymal and lumbar adipose tissue weights. Plasma levels of cholesterol, triglycerides, VLDL, glucose and insulin and leptin/adiponectin ratio were higher in HFD rats, and rosuvastatin treatment reduced them. SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 protein levels in white adipose tissue (WAT) were lower, and JNK was higher in HFD rats compared to controls. Rosuvastatin treatment normalized expression of these mediators. Endothelium-dependent relaxation was reduced in mesenteric rings from HFD rats compared to controls and rosuvastatin enhanced it in HFD rats.

Conclusion: Rosuvastatin treatment reduced insulin resistance without affecting body weight or WAT loss in HFD rats. Reduction of leptin and JNK, and enhancement of SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 expression in WAT could contribute to insulin sensitization. Normalization of SIRT-1 expression in WAT could be considered a key novel mechanism that aids in explaining the beneficial effects of rosuvastatin on the amelioration of glucose metabolism and the arrangement of multiple signaling pathways participating in insulin resistance in overweight HFD rats.

Keywords: Adipose tissue; Insulin resistance; SIRT-1; Statin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood
  • Adipokines / metabolism
  • Adipose Tissue, White / drug effects*
  • Adipose Tissue, White / immunology
  • Adipose Tissue, White / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Down-Regulation / drug effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology
  • Fluorobenzenes / therapeutic use*
  • Glucose Transporter Type 4 / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / etiology
  • Hyperlipidemias / prevention & control*
  • Insulin Resistance*
  • MAP Kinase Signaling System / drug effects
  • Male
  • Overweight / etiology
  • Overweight / immunology
  • Overweight / metabolism
  • Overweight / physiopathology*
  • PPAR gamma / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Pyrimidines / therapeutic use*
  • Rats
  • Rats, Wistar
  • Rosuvastatin Calcium
  • Sirtuin 1 / metabolism*
  • Sulfonamides / therapeutic use*
  • Transcription Factors / metabolism
  • Vasodilation / drug effects


  • Adipokines
  • Fluorobenzenes
  • Glucose Transporter Type 4
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Pyrimidines
  • Slc2a4 protein, rat
  • Sulfonamides
  • Transcription Factors
  • Rosuvastatin Calcium
  • Sirt1 protein, rat
  • Sirtuin 1