# Differential Impact of Zearalenone on Hepatic Glucose and Lipid Metabolism in Healthy and Ketotic Dairy Cows: An In Vitro Study

## TL;DR

This study shows how the mycotoxin Zearalenone affects liver metabolism differently in healthy and sick dairy cows using an in vitro model.

## Contribution

A novel in vitro model is introduced to study ZEN's effects on liver metabolism in cows with varying metabolic health.

## Key findings

- ZEN caused time- and dose-dependent changes in gene expression related to glucose and lipid metabolism.
- Hepatocytes from healthy cows showed a stronger transcriptional response to ZEN than those from ketotic cows.
- Interaction effects between ZEN dose and metabolic status were observed for genes in glycolysis and fatty acid metabolism.

## Abstract

Zearalenone (ZEN), a mycotoxin commonly present in maize-based feed, poses a health risk to dairy cows. While the hepatic effects of ZEN are increasingly studied, little is known about its impact on cows with altered energy metabolism. This study investigated the transcriptional response of liver cells isolated from healthy and ketotic cows to ZEN exposure using a novel in vitro model. Hepatocytes were obtained via biopsy from 12 cows, cultured under standardized conditions, and exposed to ZEN (0–100 µM) for 1, 3, and 6 h. Gene expression analysis focused on targets related to glucose and lipid metabolism. ZEN induced time- and dose-dependent changes in gene expression, with the most prominent effects observed after 1 h. Key metabolic genes were differentially regulated depending on the cow’s metabolic status. Notably, hepatocytes from healthy cows showed a stronger transcriptional response than those from ketotic cows, indicating reduced metabolic adaptability in energy-compromised animals. Significant interaction effects between ZEN dose and metabolic status were observed, especially for genes involved in glycolysis and fatty acid metabolism. This study presents a novel in vitro model and emphasizes the need to consider metabolic health when assessing the risks of mycotoxin exposure in dairy cattle.