Loss of the Melanocortin-4 Receptor in Mice Causes Dilated Cardiomyopathy

Overview

Journal Elife

Specialty Biology

Date 2017 Aug 23

PMID 28829041

Citations 8

Authors

Michael J Litt

G Donald Okoye

Daniel Lark

Isin Cakir

Christy Moore

Mary C Barber

James Atkinson

Josh Fessel

Javid Moslehi

Roger D Cone

Affiliations

Soon will be listed here.

Abstract

Haploinsufficiency of the melanocortin-4 receptor, the most common monogenetic obesity syndrome in humans, is associated with a reduction in autonomic tone, bradycardia, and incidence of obesity-associated hypertension. Thus, it has been assumed that melanocortin obesity syndrome may be protective with respect to obesity-associated cardiovascular disease. We show here that absence of the melanocortin-4 receptor (MC4R) in mice causes dilated cardiomyopathy, characterized by reduced contractility and increased left ventricular diameter. This cardiomyopathy is independent of obesity as weight matched diet induced obese mice do not display systolic dysfunction. cardiomyopathy is characterized by ultrastructural changes in mitochondrial morphology and cardiomyocyte disorganization. Remarkably, testing of myocardial tissue from mice exhibited increased ADP stimulated respiratory capacity. However, this increase in respiration correlates with increased reactive oxygen species production - a canonical mediator of tissue damage. Together this study identifies MC4R deletion as a novel and potentially clinically important cause of heart failure.

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