Anti-inflammatory effect of atorvastatin ameliorates insulin resistance in monosodium glutamate–treated obese mice

• Published in: Metabolism, clinical and experimental Vol. 59; no. 3; pp. 395 - 399
• Main Authors: Furuya, Daniela T, Poletto, Ana C, Favaro, Rodolfo R, Martins, Joilson O, Zorn, Telma M.T, Machado, Ubiratan F
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-03-2010; Elsevier
• Subjects: Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Adipose Tissue, White - pathology; Animals; Anti-Inflammatory Agents, Non-Steroidal; Atorvastatin Calcium; Biological and medical sciences; Blood Glucose - metabolism; Cytokines - blood; Endocrinology & Metabolism; Enzyme-Linked Immunosorbent Assay; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glucose Transporter Type 4 - biosynthesis; Glucose Transporter Type 4 - metabolism; Heptanoic Acids - therapeutic use; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; I-kappa B Kinase - biosynthesis; Immunohistochemistry; Insulin Resistance - physiology; Lipids - blood; Male; Medical sciences; Metabolic diseases; Mice; Obesity; Obesity - blood; Obesity - chemically induced; Obesity - drug therapy; Pyrroles - therapeutic use; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - genetics; Sodium Glutamate; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Endocrinopathy; Hypocholesterolemic agent; HMG-CoA reductase inhibitor; Nutritional status; Obesity; Enzyme; Rodentia; Nutrition disorder; Antiinflammatory agent; Enzyme inhibitor; Metabolic diseases; Statin derivative; Glutamate; Target tissue resistance; Vertebrata; Mammalia; Treatment; Mouse; Animal; Excitatory aminoacid; Neurotransmitter; Atorvastatin; Hydroxymethylglutaryl-CoA reductase; Insulin resistance; Oxidoreductases; Endocrinology; Antilipemic agent
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2009.08.011

Abstract Considering that inflammation contributes to obesity-induced insulin resistance and that statins have been reported to have other effects beyond cholesterol lowering, the present study aimed to investigate whether atorvastatin treatment has anti-inflammatory action in white adipose tissue of obese mice, consequently improving insulin sensitivity. Insulin sensitivity in vivo (by insulin tolerance test); metabolic-hormonal profile; plasma tumor necrosis factor (TNF)– α , interleukin (IL)-6, and adiponectin; adipose tissue immunohistochemistry; glucose transporter (GLUT) 4; adiponectin; TNF- α ; IL-1 β ; and IL-6 gene expression; and I κ B kinase (IKK)– α / β activity were assessed in 23-week-old monosodium glutamate–induced obese mice untreated or treated with atorvastatin for 4 weeks. Insulin-resistant obese mice had increased plasma triglyceride, insulin, TNF- α , and IL-6 plasma levels. Adipose tissue of obese animals showed increased macrophage infiltration, IKK- α (42%, P < .05) and IKK- β (73%, P < .05) phosphorylation, and TNF- α and IL-6 messenger RNA (mRNA) (∼15%, P < .05) levels, and decreased GLUT4 mRNA and protein (30%, P < .05) levels. Atorvastatin treatment lowered cholesterol, triglyceride, insulin, TNF- α , and IL-6 plasma levels, and restored whole-body insulin sensitivity. In adipose tissue, atorvastatin decreased macrophage infiltration and normalized IKK- α / β phosphorylation; TNF- α , IL-6, and GLUT4 mRNA; and GLUT4 protein to control levels. The present findings demonstrate that atorvastatin has anti-inflammatory effects on adipose tissue of obese mice, which may be important to its local and whole-body insulin-sensitization effects.