title: Atorvastatin improves insulin sensitivity in mice with obesity induced by monosodium glutamate.
abstract: OBJECTIVE
  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 alpha (TNF-alpha) in serum and adipose tissue in MSG obese mice. Atorvastatin treatment decreased expression of IL-6, TNF-alpha, nuclear factor kappaB (NF-kappaB) and I-kappa-B (IkappaB) kinase-beta, but increased the expression of IkappaB, in adipose tissue.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Huan
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Guang-ming
authors.initials: GM
authors.lastname: Song
authors.forename: Su-juan
authors.initials: SJ
authors.lastname: Sun
authors.forename: Zhu-fang
authors.initials: ZF
authors.lastname: Shen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000069059:Atorvastatin; D001786:Blood Glucose / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D011758:Pyrroles / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D012970:Sodium Glutamate
chemical_list: D001786:Blood Glucose; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D011758:Pyrroles; D000069059:Atorvastatin; D012970:Sodium Glutamate