Functional roles of folic acid in alleviating dexamethasone‐induced fatty liver syndrome in laying hens

Abstract

Fatty liver syndrome (FLS) poses a threat to the poultry industry due to its high occurrence and mortality rate. Folic acid (FA) is a coenzyme crucial for one‐carbon metabolism. However, the mechanism by which FA mitigates FLS in laying hens remains elusive. In this study, 60 21‐week‐old Hy‐Line Brown layers were divided into three groups: the Control (Con) group, the dexamethasone (DXM) group, and the DXM + FA group. Results showed that liver index was significantly increased in the DXM group. H&E and oil red O staining showed the accumulation of lipid droplets in the liver was intensified, confirming the successful establishment of an early fatty liver model without inflammation. FA significantly reversed hepatic lipid deposition, and 57 differentially expressed genes affected by FA were identified in the transcriptome analysis. Their transcriptional and translational levels indicate that in the early FLS, insulin‐like growth factor 2/phosphatidylinositol‐3‐kinase/protein kinase B pathway related to lipid metabolism was activated; folate cycling was inhibited, while endoplasmic reticulum (ER) stress and apoptosis‐related protein abundance were elevated. Dietary FA enhanced the folate circulation, reduced lipogenesis and ER stress, and apoptosis‐related protein expression, thereby mitigating the lipid metabolism disturbance in FLS. Metabolomics identified 151 differential metabolites involved in early FLS occurrence, 34 of which were reversed by FA. Metabolites were also enriched in pathways related to lipid metabolism and hepatic damage. Collectively, these findings can be concluded that FA can alleviate early FLS by affecting lipogenesis, ER stress and apoptosis, which may be mediated by enhanced folate metabolism.