Leptin as a cardiac hypertrophic factor: a potential target for therapeutics.
The satiety factor leptin has received extensive attention especially in terms of its potential role in appetite suppression and regulation of energy expenditure. Once considered to be solely derived from adipose tissue, which accounts for the greatly increased levels observed in obese subjects, it is now apparent that leptin can be produced by a multiplicity of tissues, including the heart, where it appears to function in an autocrine and paracrine manner. Plasma leptin concentrations are also elevated in patients with heart disease including those with congestive heart failure. Leptin exerts its biological effects via a family of receptors termed Ob-R. In cardiac cells, one of leptin's primary actions is to produce cardiomyocyte hypertrophy through multifaceted cell signaling mechanisms including stimulation of mitogen-activated protein kinase and activation of the RhoA/Rho kinase (ROCK) pathway. The hypertrophic effect of leptin suggests that it may contribute to myocardial remodeling after cardiac injury and offers the potential targeting of the leptin system as a novel cardiac therapy.
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1. morris.karmazyn@schulich.uwo.ca
Morris
M
Karmazyn
Daniel M
DM
Purdham
Venkatesh
V
Rajapurohitam
Asad
A
Zeidan
D000273:Adipose Tissue / Q000503:physiopathology*; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D020738:Leptin / Q000097:blood*; D020928:Mitogen-Activated Protein Kinases; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac; D009765:Obesity / Q000503:physiopathology*; D012307:Risk Factors; D015398:Signal Transduction
D020738:Leptin; D020928:Mitogen-Activated Protein Kinases