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Journal of Parenteral and Enteral Nutrition
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2008 Research Workshop

Adipose Inflammation, Insulin Resistance, and Cardiovascular Disease

Arti Shah, MD1, Nehal Mehta, MD1,2 and Muredach P. Reilly, MB1,2

From the 1 Department of Medicine and2 Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

Address correspondence to: Muredach P. Reilly, Cardiovascular Institute, University of Pennsylvania Medical Center, 909 BRB 2/3, 421 Curie Blvd, Philadelphia, PA 19104-6160; e-mail: muredach{at}spirit.gcrc.upenn.edu.

Adiposity-associated inflammation and insulin resistance are strongly implicated in the development of type 2 diabetes and atherosclerotic cardiovascular disease. This article reviews the mechanisms of adipose inflammation, because these may represent therapeutic targets for insulin resistance and for prevention of metabolic and cardiovascular consequences of obesity. The initial insult in adipose inflammation and insulin resistance, mediated by macrophage recruitment and endogenous ligand activation of Toll-like receptors, is perpetuated through chemokine secretion, adipose retention of macrophages, and elaboration of pro-inflammatory adipocytokines. Activation of various kinases modulates adipocyte transcription factors, including peroxisome proliferator-activated receptor-{gamma} and NF{kappa}B, attenuating insulin signaling and increasing adipocytokine and free fatty acid secretion. Inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. Paracrine and endocrine adipose inflammatory events induce a local and systemic inflammatory, insulin-resistant state promoting meta-bolic dyslipidemia, type 2 diabetes, and cardiovascular disease. Developing therapeutic strategies that target both adipose inflammation and insulin resistance may help to prevent type 2 diabetes and cardiovascular disease in the emerging epidemic of obesity.

Key Words: type 2 diabetes • insulin resistance • adiposity-associated inflammation • adipose tissue • insulin • fatty acids

Journal of Parenteral and Enteral Nutrition, Vol. 32, No. 6, 638-644 (2008)
DOI: 10.1177/0148607108325251
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