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Leptin, the obesity-associated hormone, exhibits direct cardioprotective effects

Smith, CCT; Mocanu, MM; Davidson, SM; Wynne, AM; Simpkin, JC; Yellon, DM; (2006) Leptin, the obesity-associated hormone, exhibits direct cardioprotective effects. BRIT J PHARMACOL , 149 (1) 5 - 13. 10.1038/sj.bjp.0706834. Gold open access

Abstract

Background and purpose: Protection against ischaemia-reperfusion (I/R) injury involves PI3K-Akt and p44/42 MAPK activation. Leptin which regulates appetite and energy balance also promotes myocyte proliferation via PI3K-Akt and p44/42 MAPK activation. We, therefore, hypothesized that leptin may also exhibit cardioprotective activity.Experimental approach: The influence of leptin on I/R injury was examined in perfused hearts from C57BI/6J mice that underwent 35 min global ischaemia and 35 min reperfusion, infarct size being assessed by triphenyltetrazolium chloride staining. The concomitant activation of cell-signalling pathways was investigated by Western blotting. The effect of leptin on mitochondrial permeability transition pore (MPTP) opening was studied in rat cardiomyocytes.Key results: Leptin (10 nM) administered during reperfusion reduced infarct size significantly. Protection was blocked by either LY294002 or UO126, inhibitors of Akt and p44/42 MAPK, respectively. Western blotting confirmed that leptin stimulated p44/42 MAPK phosphorylation significantly. Akt phosphorylation was also enhanced but did not achieve statistical significance. Additionally, leptin treatment was associated with a significant increase in p38 phosphorylation. By contrast, leptin caused downregulation of phosphorylated and non-phosphorylated STAT3, and of total AMP-activated kinase. Cardiomyocytes responded to leptin with delayed opening of the MPTP and delayed time until contracture.Conclusions and implications: Our data indicate for the first time that the adipocytokine, leptin, has direct cardioprotective properties which may involve the PI3-Akt and p44/42 MAPK pathways.

Type: Article
Title: Leptin, the obesity-associated hormone, exhibits direct cardioprotective effects
Open access status: An open access publication
DOI: 10.1038/sj.bjp.0706834
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC16294...
Keywords: leptin, myocardial ischaemia -reperfusion, cardiomyocytes, mitochondrial permeability transition pore, Akt, p44/ 42 MAPK, MITOCHONDRIAL PERMEABILITY TRANSITION, ISCHEMIA-REPERFUSION INJURY, ACTIVATED PROTEIN-KINASE, RAT VENTRICULAR MYOCYTES, VASCULAR SMOOTH-MUSCLE, IN-VIVO, RECEPTOR ACTIVATION, SURVIVAL KINASES, CROSS-TALK, HEART
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Hatter Cardiovascular Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/183222
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