Hydrolysis of triglycerides to fatty acids and glycerol in fat cells (lipolysis) is of importance for the control of lipid and carbohydrate metabolism. This process is regulated by several hormones and parahormones acting on cyclic AMP formation or breakdown, which in turn influences the activity of hormone sensitive lipase. The latter enzyme stimulates hydrolysis of triglycerides in fat cells. It is well established through in vivo and in vitro investigations that there are regional variations in the lipolytic activity of human adipose tissue. The rate of lipolysis is low in the subcutaneous femoral/gluteal region, intermediate in the subcutaneous abdominal region and high in the visceral (i.e. omental) region. In non-obese subjects the differences between the subcutaneous and visceral fat depots may be explained by site variations in the function of receptors for insulin, catecholamines and adenosine. The lipolytic beta₁ and beta₂ adrenoceptors, as well as the newly discovered beta₃, are most active in the visceral fat cells. The antilipolytic insulin receptors, alpha₂ adrenoceptors and adenosine receptors are most active in the subcutaneous fat cells. In subjects with upper-body obesity the regional variations in the action of catecholamines on lipolysis are further enhanced. Decreased action of beta₂-adrenergic receptors and increased activity of alpha₂-adrenergic adrenoceptors in combination with defects in hormone sensitive lipase function inhibits the lipolytic effect of catecholamines in subcutaneous fat cells whereas increased activity of beta₃-adrenergic receptors and decreased activity of alpha₂ adrenoceptors augment the lipolytic response in visceral fat cells. These abnormalities in catecholamine function promote release of free fatty acids from the visceral fat cells to the liver through the portal system and might cause several of the metabolic complications to upper-body obesity.