# Myocardial lipin1 protects the heart against ischemic injury by preserving lipid homeostasis

## TL;DR

Lipin1 helps protect the heart from damage after a heart attack by maintaining healthy lipid levels.

## Contribution

This study reveals that lipin1 protects the heart from ischemic injury by preserving lipid homeostasis.

## Key findings

- Lipin1 levels decrease in failing human hearts and ischemic mouse hearts.
- Lipin1 overexpression reduces fibrosis, inflammation, and improves heart function after MI.
- Lipin1 maintains lipid droplets and fatty acid oxidation gene expression in ischemic cardiomyocytes.

## Abstract

Impaired cardiac lipid metabolism has been reported to cause heart failure. Lipin1, a multifunctional protein, is a phosphatidate phosphatase that generates diacylglycerol from phosphatidic acid and a transcriptional cofactor that regulates lipid metabolism-related gene expression. Here, we investigated the roles of lipin1 in cardiac remodeling after myocardial infarction (MI). The expression levels of lipin1 significantly decreased in cardiomyocytes of the human failing heart and murine ischemic myocardium. Cardiomyocyte-specific Lpin1 knockout (cKO) mice showed left ventricle enlargement and reduced fractional shortening after MI, compared with control mice. This was accompanied by elevated cardiac fibrosis, accumulation of reactive oxygen species, and increased expression of inflammatory cytokines. In contrast, cardiomyocyte-specific Lpin1 overexpression (cOE) mice showed reduced fibrosis and inflammation and improved cardiac function compared with control mice. Cardiac lipid droplets (LDs) were reduced after MI in WT mouse hearts and were further downregulated in the hearts of cKO mice with a decrease in triacylglycerol and free fatty acid content, while cOE mice hearts exhibited increased LDs and lipid content. Expression levels of genes involved in fatty acid oxidation, such as Ppargc1a (PGC1A) and Acaa2, were decreased and increased in the MI hearts of cKO mice and cOE mice, respectively. These results suggest the protective role of lipin1 against ischemic injury by maintaining lipid metabolism in ischemic cardiomyocytes.

Myocardial lipin1 protects the heart from ischemic injury by regulating lipid metabolism.