# Farnesol Improves Endoplasmic Reticulum Stress and Hepatic Metabolic Dysfunction Induced by Tunicamycin in Mice

## TL;DR

Farnesol reduces liver damage and metabolic issues caused by tunicamycin in mice, suggesting it could be a natural treatment for liver diseases.

## Contribution

Farnesol's ability to counteract tunicamycin-induced ER stress and restore liver metabolism is newly demonstrated in both cell and animal models.

## Key findings

- Farnesol reduced ER stress markers like ATF4 and restored metabolic gene expression in liver cells.
- In mice, farnesol alleviated oxidative stress, lipid accumulation, and preserved liver structure.
- Farnesol improved serum lipid profiles and modulated metabolic biomarkers in tunicamycin-treated mice.

## Abstract

This study investigated the potential of farnesol (FOH), a natural compound found in essential oils, to protect the liver from stress induced by tunicamycin (TM), a substance known to disrupt cellular processes and contribute to liver diseases. TM causes oxidative stress, lipid accumulation, and alters liver function, leading to metabolic disorders such as fatty liver disease. In this study, both liver cells and animal models were treated with TM to simulate these conditions. The findings show that FOH could reduce the harmful effects of TM, restoring normal liver function, reducing fat accumulation, and preserving healthy liver structure. This study highlights FOH’s potential as a natural therapy for liver diseases linked to metabolic stress.

Endoplasmic reticulum (ER) stress significantly affects liver metabolism, often leading to disorders such as hepatic steatosis. Tunicamycin (TM), a known ER stress inducer, is frequently used to model metabolic stress, but its specific effects on liver energy homeostasis remain unclear. This study investigates how farnesol (FOH), a natural compound with antioxidant and anti-inflammatory properties, counteracts TM-induced ER stress and its associated metabolic disruptions in the liver. Using both primary hepatocytes and a mouse model, this study demonstrates that TM treatment caused upregulation of ER stress markers, including ATF4, and disrupted genes related to lipid metabolism and gluconeogenesis. Co-treatment with FOH reduced these stress markers and restored the expression of metabolic genes. In vivo, FOH treatment alleviated oxidative stress, reduced lipid accumulation, and restored normal glycogen and lipid metabolism. Histological analysis further confirmed that FOH preserved liver architecture and minimized cellular damage. FOH also stabilized serum lipid profiles and modulated key metabolic biomarkers, suggesting its protective role against TM-induced liver injury. These findings suggest that FOH has therapeutic potential in mitigating ER stress-related metabolic dysfunctions, offering promising insights for the treatment of liver diseases linked to metabolic stress.