ABSTRACT
Leptin, initially identified as the product o f the obesity gene in 1994, has received extensive attention especially in terms o f its potential role in appetite suppression and regulation o f energy expenditure. Leptin is primarily produced by white adiposity tissue and the polypeptide exerts its principal effects on the hypothalamus by acting on its receptors, termed LR or OBR. Plasma leptin levels are greatly elevated in obese individuals which has been closely related to the degree o f adiposity. A lthough once considered to be solely derived from adipose tissue it is now apparent that leptin can be produced by various tissues including those compris ing the cardiovascular system. Moreover, identification o f LR expression has been demonstrated in numerous cardiovascular tissue as well as blood borne factors such as platelets suggesting that leptin exerts biological effects beyond those initially identified and related to appetite suppres sion. In terms o f the cardiovascular system LR have been identified in both vascular and cardiac tissues. The increased cardiovascular risk associated w ith obesity is well known and many o f the effects o f leptin appear to be compatible w ith its potential role as a contributing factor to increased cardiovascular m orbidity associated with obesity. In both myocardial and vascular tissues leptin exerts its effects via multifaceted cell signalling mechanisms. In terms o f leptin s ability to produce vascular or cardiomyocyte hypertrophy or hyperplasia the effects appear to M APK-dependent. Recent evidence suggests that p38 activation is o f particular importance although how this occurs is uncertain. Leptin also activates the R hoA /R O C K pathway resulting in altered actin dynamics which in turn may be im portant to p38 activation resulting in hypertrophy. Understanding the cell signalling mechanisms underlying the effects o f leptin is o f major importance in terms o f developing therapeutic intervention targeting the leptin system as a novel approach for treating cardiovascular disorders, particularly those associated w ith hyperleptinemia.
