Restoration of Cardiac Function After Myocardial Infarction by Long-Term Activation of the CNS Leptin-Melanocortin System

Fabio N Gava; Alexandre A da Silva; Xuemei Dai; Romain Harmancey; Sadia Ashraf; Ana C M Omoto; Mateus C Salgado; Sydney P Moak; Xuan Li; John E Hall; Jussara M do Carmo

doi:10.1016/j.jacbts.2020.11.007

Restoration of Cardiac Function After Myocardial Infarction by Long-Term Activation of the CNS Leptin-Melanocortin System

JACC Basic Transl Sci. 2021 Jan 25;6(1):55-70. doi: 10.1016/j.jacbts.2020.11.007. eCollection 2021 Jan.

Authors

Fabio N Gava^{1

2}, Alexandre A da Silva¹, Xuemei Dai¹, Romain Harmancey¹, Sadia Ashraf¹, Ana C M Omoto^{1

3}, Mateus C Salgado^{1

4}, Sydney P Moak¹, Xuan Li¹, John E Hall¹, Jussara M do Carmo¹

Affiliations

¹ Department of Physiology and Biophysics and Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
² Department of Veterinary Clinics, Londrina State University, Parana, Brazil.
³ Department of Physiology, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
⁴ Centro Universitário Barão de Mauá, Ribeirão Preto, São Paulo, Brazil.

Abstract

Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca²⁺ coupling, and mitochondrial efficiency. These findings highlight a potentially novel therapeutic approach for myocardial infarction and heart failure.

Keywords: AMPK, adenosine monophosphate–activated protein kinase; BP, blood pressure; CNS, central nervous system; HF, heart failure; HR, heart rate; ICV, intracerebroventricular; LV, left ventricular; MC4R; MC4R, melanocortin-4 receptor; MI, myocardial infarction; MTII, melanotan II; appetite; blood pressure; cardiac metabolism; heart failure; mTOR, mechanistic target of rapamycin.

Abstract

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