Lipid-induced cell stress and insulin resistance

Abstract

In our Westernized society, although some excess body fat is stored inside its proper place, adipose tissue, the surplus of circulating fatty acids is also excessively stored in the liver, heart, pancreas and skeletal muscle. In these tissues, intracellular fat accumulation, in combination with a low oxidative capacity, is associated with decreased insulin sensitivity. Although the exact mechanism behind the negative effect of intracellular lipid accumulation on insulin sensitivity has not been completely unravelled, ample evidence suggests that fatty acid intermediates, such as diacylglycerol, fatty acyl-coenzyme-A and ceramides, can hamper insulin signalling. However, recent evidence also points towards a role for reactive oxygen species in the development of insulin resistance. The present review will focus on how fatty acids in combination with oxidative stress can lead to lipid-induced oxidative damage, thereby impairing mitochondrial function and facilitating the accumulation of muscular lipids. © 2006 Taylor & Francis.