# Seipin‐Mediated Lipid Droplet Formation in Cardiomyocytes Ameliorates Cardiac Ischemia/Reperfusion Injury

## TL;DR

Lipid droplets help protect the heart during ischemia/reperfusion injury, and increasing them through Seipin improves outcomes.

## Contribution

The study reveals Seipin's role in LD formation and its therapeutic potential for cardiac I/R injury.

## Key findings

- Seipin deficiency reduces LD levels and worsens cardiac I/R injury.
- Increasing LD levels via Seipin overexpression or lipolysis inhibition ameliorates I/R injury.
- USF1 regulates Seipin expression during acute myocardial ischemia.

## Abstract

Cardiac ischemia/reperfusion (I/R) injury is an important therapeutic target for ischemic heart disease. Lipid droplets (LDs) are the key organelles involved in lipid metabolism. This study aimed to identify the LD‐mediated protection against lipotoxicity in cardiac I/R injury. LD accumulation is upregulated in hearts subjected to I/R injury; however, it is insufficient to neutralize lipotoxicity or prevent cardiomyocyte death. Seipin played a central role in LD biogenesis in cardiomyocytes following I/R injury. Seipin deficiency led to reduced LD levels and exacerbated cardiac I/R injury. Whereas increased LD levels, via Seipin overexpression or lipolysis inhibition, ameliorated myocardial I/R injury. I/R‐induced downregulation of Seipin is attributed to the reduced expression of its transcription factor USF1, which is required for metabolic adaptation in acute myocardial ischemia. These findings not only elucidate the pathophysiological roles of LDs and Seipin but also provide a promising therapeutic target for myocardial I/R injury.

Lipid droplets (LDs) protect the heart against lipotoxicity in cardiac ischemia/reperfusion (I/R) injury; however, they are insufficient to prevent cardiomyocyte death. Seipin plays a central role in the insufficient formation of LDs, subsequent lipotoxicity, and myocardial injury during cardiac I/R injury. Genetic or pharmacological treatments to improve LDs levels could alleviate I/R‐induced cardiomyocyte death and myocardial injury.