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(Circulation Research. 2007;100:1531.)
© 2007 American Heart Association, Inc.

Editorials

Innate Immune Pathway Links Obesity to Insulin Resistance

Prediman K. Shah

From the Division of Cardiology and Atherosclerosis Research Center, Burns and Allen Research Institute and the Department of Medicine, Cedars Sinai Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, Calif.

Correspondence to P.K. Shah, MD, Director, Division of Cardiology and Atherosclerosis Research Center, Cedars Sinai Medical Center, Suite 5531, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail shahp@cshs.org

See related article, pages 1589–1596

Key Words: obesity • insulin resistance • toll like receptor • inflammation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The prevalence of obesity, especially among adolescents, has increased considerably over the past 20 years because of increased caloric intake and reduced physical activity. It has been estimated that 20% of the world’s population is overweight and nearly 300 million are obese (BMI >30 kg/m²).^1,2 Excess body weight and obesity are associated with the development of metabolic syndrome and type II diabetes, both of which are associated with insulin resistance and increased risk of cardiovascular complications.^1,2

Atherothrombotic vascular disease, resulting from a complex interplay between dyslipidemia and vascular immunoinflammatory processes, is responsible for a majority of the excess morbidity and mortality that characterizes metabolic syndrome and type II diabetes.^1,2 Several studies have shown that obesity is associated with activation of inflammatory pathways and that inflammatory responses are associated with impaired insulin signaling and insulin resistance.^3–8 Considerable progress has been made in the last 2 decades in our understanding of molecular events that link obesity to inflammation, insulin resistance, type II diabetes, and enhanced vascular disease. Obesity-mediated skeletal muscle insulin resistance has been linked to defects in cellular signaling events triggered by insulin.^3–8 In obesity, the skeletal muscle levels of several kinases such as protein kinase C isoforms (PKC), I Kappa B Kinase-ß (IKK-ß), and c-jun–terminal kinase (JNK) are elevated, and these kinases have been implicated in suppression of insulin signaling by promoting serine phosphorylation of insulin receptor substrate (IRS) which is associated with suppression of tyrosine phosphorylation of IRS (Figure).¹ Several studies have shown that nutrient excess . . . [Full Text of this Article]

Related Article:

Toll-Like Receptor-4 Mediates Vascular Inflammation and Insulin Resistance in Diet-Induced Obesity

Francis Kim, Matilda Pham, Ian Luttrell, Douglas D. Bannerman, Joan Tupper, Joshua Thaler, Thomas R. Hawn, Elaine W. Raines, and Michael W. Schwartz
Circ. Res. 2007 100: 1589-1596. [Abstract] [Full Text] [PDF]

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