Obesity, insulin resistance and free fatty acids

Abstract

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.

Figure 1

Relationship between positive energy balance, an expanded adipose tissue (obesity), insulin resistance and cardiovascular disease. A chronic positive energy balance results in an expanded adipose tissue, i.e., obesity and is associated with insulin resistance and the development of serious disorders including type 2 diabetes, hypertension, dyslipidemia and disorders of coagulation and fibrinolysis which are all independent risk factors for the development of cardiovascular disease.