Abstract
Since its initial discovery as a satiety product of the obesity gene, leptin has received extensive attention especially in terms of its potential role in appetite suppression and regulation of energy expenditure. The primary sources of leptin production are adipocytes and the peptide exerts its principal effects on the hypothalamus by acting on its receptors, termed OBR. Plasma leptin levels are greatly elevated in obese individuals and this finding has been closely related to the degree of adipocity. Although once considered to be solely derived from adipose tissue, it is now apparent that leptin can be produced by various tissues including those comprising the cardiovascular system. Moreover, identification of OBR expression has been demonstrated in numerous cardiovascular tissues as well as bloodborne factors such as platelets suggesting that leptin exerts biological effects beyond those initially identified and related to appetite suppression. In terms of the cardiovascular system, OBR have been identified in both vascular and cardiac tissues. The increased cardiovascular risk associated with obesity is well known and many of the effects of leptin appear to be compatible with its potential role as a contributing factor to increased cardiovascular morbidity associated with obesity. In both myocardial and vascular tissues, leptin exerts its effects via multifaceted cell signaling mechanisms. In terms of leptin’s ability to produce vascular or cardiomyocyte hypertrophy or hyperplasia, the effects appear to MAPK-dependent. Recent evidence suggests that p38 activation is of particular importance although how this occurs is uncertain. Leptin also activates the RhoA/ROCK pathway resulting in altered actin dynamics which in turn may be important to p38 activation resulting in hypertrophy. Understanding the cell signaling mechanisms underlying the effects of leptin is of major importance in terms of developing therapeutic intervention targeting the leptin system as a novel approach for treating cardiovascular disorders, particularly those associated with hyperleptinemia.
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Karmazyn, M., Purdham, D.M., Rajapurohitam, V., Zeidan, A. (2008). Leptin Signaling in the Cardiovascular System. In: Srivastava, A.K., Anand-Srivastava, M.B. (eds) Signal Transduction in the Cardiovascular System in Health and Disease. Advances in Biochemistry in Health and Disease, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-09552-3_20
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