[Study of the mechanisms of insulin resistance in obesity]. It is now well accepted that insulin resistance is a fundamental defect in obesity and contributes to obesity-associated insulin resistance. Insulin resistance may be caused by several factors, most of them linked to obesity. Decreased glucose transporter-4 (GLUT4) protein content on cell surface is a new mechanism responsible for decreased insulin sensitivity. The GLUT4 is highly expressed in adipose tissue. In the obese adipose tissue GLUT4 expression and the GLUT4 plasma membrane content are decreased. The decrease of GLUT4 in the adipose tissue is not explained by a decrease of GLUT4 gene expression in the adipose tissue. Instead, it seems to be due to decreased transcription of GLUT4. This defect may be mediated by intracellular signalling pathways, including phosphoinositol-3-kinase, protein kinase C and mitogen-activated protein kinases. Insulin may also contribute to decreased GLUT4 expression in the adipose tissue by acting via the mitogen-activated protein kinases or other signalling pathways. Other mechanisms of insulin resistance include a decrease in adipose triglyceride lipase activity, a reduced glucose transporter 1 and increased fatty acid synthase expression. The role of some hormones, such as catecholamines or glucocorticoids in insulin resistance remains to be clarified. Nevertheless, new molecular mechanisms are implicated in the pathogenesis of insulin resistance in obesity. These new aspects of insulin resistance could lead to new therapies and prevention in obesity.