# Surfactant protein A promotes western diet-induced hepatic steatosis and fibrosis in mice

## TL;DR

This study shows that Surfactant Protein A worsens liver disease in mice on a high-fat diet by promoting fat buildup and inflammation.

## Contribution

The study reveals a novel role of Surfactant Protein A in promoting MASLD progression in mice.

## Key findings

- SPA deficiency reduced lipid accumulation and inflammation in mice livers.
- SPA−/− mice showed less liver fibrosis and stellate cell activation.
- SPA promotes fatty acid uptake and contributes to MASLD pathogenesis.

## Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) remains the most common cause of liver disease in the United States due to the increased incidence of metabolic dysfunction and obesity. Surfactant protein A (SPA) regulates macrophage function, strongly binds to lipids, and is implicated in renal and idiopathic pulmonary fibrosis (IPF). However, the role of SPA in lipid accumulation, inflammation, and hepatic fibrosis that characterize MASLD remains unknown. SPA deficient (SPA−/−) and age-matched wild-type (WT) control mice were fed a Western diet for 8 weeks to induce MASLD. Blood and liver samples were collected and used to analyze pathological features associated with MASLD. SPA expression was significantly upregulated in livers of mice with MASLD. SPA deficiency attenuated lipid accumulation along with downregulation of genes involved in fatty acid uptake and reduction of hepatic inflammation as evidenced by the diminished macrophage activation, decreased monocyte infiltration, and reduced production of inflammatory cytokines. Moreover, SPA−/− inhibited stellate cell activation, collagen deposit, and liver fibrosis. These results highlight the novel role of SPA in promoting fatty acid uptake into hepatocytes, causing excessive lipid accumulation, inflammation, and fibrosis implicated in the pathogenesis of MASLD.