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Updated: Jun 10, 2026
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Published on: August 9, 2022
Inhibition of cardiac leptin expression after infarction reduces subsequent dysfunction
C Moro1, S Grauzam, O Ormezzano
1Laboratoire TIMC-IMAG, UMR 5525 CNRS - University of Grenoble, Grenoble, France.
Insights
This study shows that cardiac leptin increases after heart attack (myocardial infarction) and contributes to heart failure. Inhibiting leptin protects heart function and reduces inflammation.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Leptin, an adipokine, is known to cause cardiodepressive effects and left ventricular (LV) remodeling.
- The specific roles of autocrine/paracrine leptin activity in post-myocardial infarction (MI) dysfunction and remodeling remain unclear.
Purpose of the Study:
- To investigate the changes in myocardial leptin expression after MI.
- To evaluate the impact of inhibiting cardiac leptin on LV dysfunction following MI.
Main Methods:
- Rats underwent temporary coronary occlusion to induce MI.
- Antisense oligodesoxynucleotide (AS ODN) against leptin mRNA was injected into the infarct border.
- Echocardiography monitored cardiac function and morphometry for 11 weeks.
- ELISA measured myocardial leptin and pro-inflammatory cytokines (IL-1β, IL-6).
Main Results:
- Cardiac leptin levels peaked 7 days post-MI.
- Leptin AS ODN injection reduced early overexpression of IL-1β and IL-6.
- Leptin inhibition significantly protected cardiac contractile function.
Conclusions:
- Cardiac leptin expression post-MI may drive heart failure progression via autocrine/paracrine mechanisms.
- Leptin's detrimental effects appear mediated by pro-inflammatory cytokines like IL-1β and IL-6.
- These findings suggest leptin inhibition as a potential therapeutic strategy for improving post-MI outcomes.
Abstract:
Leptin is known to exert cardiodepressive effects and to induce left ventricular (LV) remodelling. Nevertheless, the autocrine and/or paracrine activities of this adipokine in the context of post-infarct dysfunction and remodelling have not yet been elucidated. Therefore, we have investigated the evolution of myocardial leptin expression following myocardial infarction (MI) and evaluated the consequences of specific cardiac leptin inhibition on subsequent LV dysfunction. Anaesthetized rats were subjected to temporary coronary occlusion. An antisense oligodesoxynucleotide (AS ODN) directed against leptin mRNA was injected intramyocardially along the border of the infarct 5 days after surgery. Cardiac morphometry and function were monitored by echocardiography over 11 weeks following MI. Production of myocardial leptin and pro-inflammatory cytokines interleukin (IL)-1β and IL-6 were assessed by ELISA. Our results show that (1) cardiac leptin level peaks 7 days after reperfused MI; (2) intramyocardial injection of leptin-AS ODN reduces early IL-1β and IL-6 overexpression and markedly protects contractile function. In conclusion, our findings demonstrate that cardiac leptin expression after MI could contribute to the evolution towards heart failure through autocrine and/or paracrine actions. The detrimental effect of leptin could be mediated by pro-inflammatory cytokines such as IL-1β and IL-6. Our data could constitute the basis of new therapeutic approaches aimed to improve post-MI outcome.
