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Obesity, insulin resistance and free fatty acids

Boden, Guenther

Current Opinion in Endocrinology, Diabetes & Obesity: April 2011 - Volume 18 - Issue 2 - p 139–143
doi: 10.1097/MED.0b013e3283444b09
Lipids: Edited by Annabelle Rodriguez

Purpose of review: To describe the role of free fatty acid (FFA) as a cause for insulin resistance in obese people.

Recent findings: Elevated plasma FFA levels can account for a large part of insulin resistance in obese patients with type 2 diabetes. Insulin resistance is clinically important because it is closely associated with several diseases including type 2 diabetes, hypertension, dyslipidemia and abnormalities in blood coagulation and fibrinolysis. These disorders are all independent risk factors for cardiovascular disease (heart attacks, strokes and peripheral arterial disease). The mechanisms by which FFA can cause insulin resistance, although not completely known, include generation of lipid metabolites (diacylglycerol), proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP1) and cellular stress including oxidative and endoplasmic reticulum stress.

Summary: Increased plasma FFA levels are an important cause of obesity-associated insulin resistance and cardiovascular disease. Therapeutic application of this knowledge is hampered by the lack of readily accessible methods to measure FFA and by the lack of medications to lower plasma FFA levels.

Division of Endocrinology, Diabetes, Metabolism and the Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

Correspondence to Guenther Boden, MD, 3401 North Broad Street, Philadelphia, PA 19140, USA Tel: +1 215 707 8984; fax: +1 215 707 1560; e-mail: bodengh@tuhs.temple.edu

© 2011 Lippincott Williams & Wilkins, Inc.