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Leptin, the obesity‐associated hormone, exhibits direct cardioprotective effects
Open accessAbstract
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 C57Bl/6 J 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 n M) 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. British Journal of Pharmacology (2006) 149, 5–13. doi:10.1038/sj.bjp.0706834
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“Thus leptin administration has been shown to reduce infarct size and enhance myocardial functional recovery following coronary artery ligation in mice (4, 326).”
From Cardiac remodeling in obesity (2008) · cites this paper as [326]
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“Notably, leptin administration in mice has been shown to reduce infarct size and enhance functional recovery following coronary artery ligation (4, 326).”
From Cardiac remodeling in obesity (2008) · cites this paper as [326]
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Metadata
- Authors
- Smith, C. C. T., Mocanu, M. M., Davidson, S. M., Wynne, A. M., Simpkin, J. C., & Yellon, D. M.
- Affiliations
- University College Hospital (GB)
- Corresponding author
- Yellon, D M
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2006-09
- Volume
- 149
- Issue
- 1
- Pages
- 5-13
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1629412
- OpenAlex
- W2101663612
- Cited by
- 153
- References
- 49
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 9 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 11 · 2014: 12 · 2013: 7 · 2012: 13
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- leptin, cardioprotection, ischemia-reperfusion injury, myocardial infarct size, PI3K/Akt signaling, p44/42 MAPK, p38 MAPK, STAT3, AMPK, mitochondrial permeability transition pore, cardiomyocytes, adipokines, obesity
- MeSH terms
- Animals, Cardiotonic Agents, Male, Mice, Inbred C57BL, Mitochondria, Heart, Myocardium, Phosphorylation, Blotting, Western, Signal Transduction, Myocardial Reperfusion Injury, Rats, Sprague-Dawley, Oxidative Stress, Leptin, Myocytes, Cardiac, Mice, Rats, In Vitro Techniques
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