Regulation of lipolysis: natriuretic peptides and the development of cachexia

The development of cachexia is commonly seen in many pathological states and is associated with a markedly impaired prognosis. Loss of fat tissue appears to be of particular pathophysiological importance in this setting. Lipolysis is closely regulated in health; the major established pathways involving catecholamines (stimulation of lipolysis) and insulin (inhibition of lipolysis). The wasting process in cachexia is associated with marked metabolic dysfunction, and loss of this tight regulatory control. Natriuretic peptides are a family of related peptides with important vasodilatory, natriuretic and diuretic properties. It has recently been shown that natriuretic peptides are also potent stimuli for lipolysis in humans. In this respect, atrial and brain natriuretic peptide appear to have the greatest lipolytic effect, and are similar in potency to catecholamines. Elevated levels of circulating natriuretic peptides are found in several pathological states, and generally reflect disease severity. This article will provide a concise review of the regulation of lipolysis in humans, concentrating on the role of the natriuretic peptides. The relevance of natriuretic peptides to the development of cachexia will be discussed.