Millennium fat-cell lipolysis reveals unsuspected novel tracks

Adipose tissue lipolysis, i.e., the catabolic process leading to the breakd own of triglycerides into fatty acids and glycerol, is often considered as a simple and well-understood metabolic pathway. However, progress on the ho rmonal regulation and molecular mechanism of fat-cell lipolysis is opening new avenues and points to a number of unanswered questions. Recent studies on the lipolytic beta- and antilipolytic alpha (2)-adrenergic control of li polysis has allowed a better understanding of the relative contribution of the two types of receptors and provide strong evidence for the in vivo impl ication of alpha (2)-adrenoceptors in the physiological control of subcutan eous adipose-tissue lipolysis. A novel lipolytic system has been characteri zed in human fat cells. Natriuretic peptides stimulate lipolysis through a cGMP-dependent pathway. The molecular details of the lipolytic reaction are not fully understood. Translocation of hormone-sensitive lipase, the rate- limiting enzyme of lipolysis, to the lipid droplet seems to be an important step during lipolytic activation. Reorganization of the lipid droplet coat ing by perilipins may also facilitate the access of the enzyme. Unexpectedl y, hormone-sensitive lipase-deficient mice are not obese and show residual adipose-tissue lipolysis, which suggests the existence of another triglycer ide lipase. Whether the expression of this uncharacterized neutral lipase i s compensatory for the lack of hormone-sensitive lipase is an important que stion yet to be resolved. In humans, alterations of hormone-sensitive lipas e expression are associated with changes in lipolysis in various physiologi cal and pathological states. Genetic studies show that beta (2)-adrenocepto r and hormone-sensitive lipase genes may participate in the polygenic backg round of obesity.