Acta Pharmacologica Sinica (2010) 31: 102–110; doi: 10.1038/aps.2009.181

Acta Pharmacologica Sinica (2010) 31: 102–110; doi: 10.1038/aps.2009.181; published online 28 December 2009

Original Article

Atorvastatin improves insulin sensitivity in mice with obesity induced by monosodium glutamate

Heng-tong HU¹, Qing-yong MA^1,*, Dong ZHANG¹, Su-gang SHEN¹, Liang HAN¹, Ya-dong MA², Ruo-fei LI³, Ke-ping XIE⁴

¹Department of HepatobiliarySurgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, China; ²Department of Urinary Surgery, The Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710004, China; ³Department of Osteological Surgery, The Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710004, China; ⁴Department of Cancer Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA

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

We thank the staff of the Biology and Genetics Laboratory, Xi’an Jiaotong University for their technical assistance in these studies.

* To whom correspondence should be addressed.
E-mail qyma56@mail.xjtu.edu.cn
Received 2009-06-10 Accepted 2009-11-17

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