# Metabolic Dysregulation in Laminopathies: Implications for Heart Failure and Cardiac Health

## TL;DR

This review explores how metabolic issues in laminopathies contribute to heart failure and suggests targeting metabolism could improve cardiac health.

## Contribution

The paper introduces a unified metabolic perspective on laminopathies, linking metabolic dysregulation to cardiac outcomes across diverse laminopathy types.

## Key findings

- Metabolic dysregulation, including lipodystrophy and insulin resistance, is common in laminopathies before cardiac symptoms appear.
- LMNA variants disrupt fatty acid oxidation and mitochondrial function, increasing cardiomyocyte vulnerability.
- Targeting metabolic pathways shows potential for improving cardiac outcomes in laminopathy patients.

## Abstract

Laminopathies are a diverse group of genetic disorders caused by variants in nuclear lamina proteins, with heart failure being a major cause of morbidity and mortality in patients. By shifting the perspective from distinct clinical phenotypes to a continuous spectrum of metabolic observations in laminopathies, this review aims to elucidate the molecular mechanisms underlying metabolic dysregulation in laminopathies and their impact on cardiac health.

Emerging evidence links A-type lamins to cellular metabolism, with systemic metabolic changes such as lipodystrophy, insulin resistance and hypertriglyceridemia often detected in laminopathy patients before cardiac symptoms onset. At the molecular level, LMNA variants disrupt the regulation of genes involved in fatty acid, oxidation glucose utilization, and mitochondrial function. These disturbances increase cardiomyocyte susceptibility, promoting fibrosis and apoptosis.

Metabolic dysregulation is a recurring observation across the laminopathy spectrum. Targeting metabolic pathways shows preclinical promise for improving cardiac outcomes in patients.