# Molecular remodeling of the myocardium in mice with melanocortin-4 receptor deletion before cardiac function impairment

## TL;DR

This study explores how deleting the melanocortin-4 receptor gene in mice leads to early molecular changes in the heart before visible heart function issues arise.

## Contribution

The study identifies early molecular changes and potential drug targets in the heart due to Mc4r deletion, offering insights for early prevention of heart disease.

## Key findings

- Mc4r knockout in mice leads to early molecular changes in cardiomyocytes before visible heart dysfunction.
- Differentially expressed genes are enriched in p53 and HIF-1 signaling pathways.
- Angiotensinogen (Agt) and Kit are identified as potential drug targets for early heart disease prevention.

## Abstract

The melanocortin-4 receptor (MC4R) is highly expressed in the hypothalamus, and mutations in this gene are closely associated with the development of hereditary obesity and early-onset severe obesity in humans. Mc4r has been shown to be involved in the development of dilated cardiomyopathy. However, the current system for the early diagnosis and treatment of heart disease is not well established. In this study, we analyzed the effects of Mc4r knockout on cardiac function, cardiomyocyte morphology, fibrosis, and apoptosis in mice. Moreover, we explored the possible early molecular mechanisms by which Mc4r affects cardiac dysfunction via transcriptome sequencing of cardiac cells combined with bioinformatics analysis. Although the overall heart does not show organic changes, our study suggested that cardiomyocytes already show early abnormal changes at the molecular level. The sequencing results revealed that the genes that were differentially expressed between the two groups of mice were enriched mainly in the p53 signaling pathway and the hypoxia-inducible factor 1 (HIF-1) signaling pathway. We screened 10 key target genes via a protein–protein interaction (PPI) network and module analysis. Drugs targeting key genes were subsequently screened, and angiotensinogen (Agt) and Kit were identified as potential drug targets. We analyze relevant data through bioinformatics to screen for signaling pathways and key hub genes that are enriched in differentially expressed genes (DEGs), as well as molecules targeting the hub genes, in order to provide ideas for early prevention of heart disease caused by Mc4r gene defects or related obesity.