# Ferulic Acid Attenuates Heat Stress-Induced Hepatic and Intestinal Oxidative Stress and Cholesterol Metabolism Dysregulation in Juvenile Blunt Snout Bream (Megalobrama amblycephala)

## TL;DR

Ferulic acid helps reduce liver and intestinal damage from heat stress in juvenile blunt snout bream by lowering oxidative stress and improving cholesterol metabolism.

## Contribution

This study reveals the molecular mechanisms by which ferulic acid mitigates heat stress effects on oxidative stress and cholesterol metabolism in fish.

## Key findings

- Ferulic acid reduced oxidative stress markers and inflammatory gene expression in fish under heat stress.
- Ferulic acid restored cholesterol metabolism and stabilized intestinal microbiota disrupted by heat stress.
- Ferulic acid modulated metabolite profiles in plasma and intestinal contents related to cholesterol metabolism.

## Abstract

Ferulic acid (FA) is a green feed additive. To investigate the molecular mechanisms by which FA attenuates heat stress-induced hepatic and intestinal oxidative stress, as well as cholesterol metabolism disorders in Megalobrama amblycephala (9.75 ± 0.04 g), individuals were fed diets supplemented with 0, 100, or 200 mg/kg FA for eight weeks, followed by exposure to heat stress at 34 °C for 48 h. The results indicated that FA supplementation reduced malondialdehyde levels and downregulation genes involved in inflammatory responses (e.g., interleukin-6), apoptosis (e.g., caspase 8), and endoplasmic reticulum stress (e.g., immunoglobulin binding protein) (p < 0.05), which collectively alleviated heat stress-induced hepatic and intestinal oxidative stress. FA supplementation increased the expression of ATP-binding cassette transporter A1, apolipoprotein A1, and liver X receptor α (p < 0.05), and restored liver and plasma TC levels to pre-stress levels (p < 0.05). Additionally, FA ameliorated the heat stress-induced dysbiosis of the intestinal microbiota and modulated the composition and abundance of metabolites in intestinal contents and plasma, some of which are associated with cholesterol metabolism. In conclusion, dietary FA can alleviate heat stress-induced hepatic and intestinal oxidative stress, maintain the stability of the intestinal microbiota and regulate metabolic profiles, and improve the cholesterol metabolism disorders caused by heat stress.