Atorvastatin improves insulin sensitivity in mice with obesity induced by monosodium glutamate.
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.
Zhang
Ning
N
Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
Huan
Yi
Y
Huang
Hui
H
Song
Guang-ming
GM
Sun
Su-juan
SJ
Shen
Zhu-fang
ZF
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
D001786:Blood Glucose; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D011758:Pyrroles; D000069059:Atorvastatin; D012970:Sodium Glutamate