Acta Pharmacologica Sinica (2010) 31: 35–42; doi: 10.1038/aps.2009.176; published online 21 December 2009

Ning ZHANG, Yi HUAN, Hui HUANG, Guang-ming SONG, Su-juan SUN, Zhu-fang SHEN*

Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China

Aim: To examine the mechanisms underlying the effects of atorvastatin on glucose and lipid metabolism. 

Methods: Mice with insulin resistance and obesity induced by monosodium glutamate (MSG) were used.  Atorvastatin (80 mg·kg^-1·d^-1) or vehicle control treatment was given orally once a day for 30 days.  Plasma levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and free fatty acids were monitored.  Serum insulin and glucose concentrations were used to calculate the insulin resistance index and insulin sensitivity index using a homeostasis model.  Body length, waistline circumference, intraperitoneal adipose tissue mass, and total body mass were measured.  Semi-quantitative RT-PCR and Western analysis were used to determine the expression of inflammatory factors and proteins involved in inflammation signaling pathways.

Results: Atorvastatin improved insulin sensitivity, ameliorated glucose tolerance, and decreased plasma levels of total cholesterol, triglycerides, LDL-C, HDL-C and free fatty acids.  Semi-quantitative RT-PCR and Western analysis revealed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in serum and adipose tissue in MSG obese mice.  Atorvastatin treatment decreased expression of IL-6, TNF-α, nuclear factor κB (NF-κB) and I-kappa-B (IκB) kinase-β, but increased the expression of IκB, in adipose tissue.

Conclusion: Atorvastatin is a potential candidate for the prevention and therapy of diseases associated with insulin resistance such as type 2 diabetes mellitus and cardiovascular disease. One possible mechanism underlying the effects of atorvastatin on glucose and lipid metabolism may be to ameliorate a state of chronic inflammation.

Keywords: atorvastatin; insulin resistance; HMG-CoA reductase inhibitor; monosodium glutamate; obesity