# Elucidating the Molecular Basis of Thermal Stress Response in Juvenile Turbot (Scophthalmus maximus) via an Integrative Transcriptome–Metabolome Approach

## TL;DR

This study explores how juvenile turbot respond to heat stress at the molecular level, using gene and metabolite analysis to identify key pathways involved in thermal adaptation.

## Contribution

The study provides new insights into the molecular mechanisms of thermal stress response in turbot through an integrative transcriptome-metabolome approach.

## Key findings

- Thermal stress significantly alters gene expression and metabolite profiles in turbot liver.
- Key pathways like PI3K-Akt signaling and amino acid metabolism are crucial for thermal adaptation.
- Genes such as CDH1, Col9a1, and DNAJB6 are linked to specific metabolic changes under heat stress.

## Abstract

High temperatures can induce tissue damage and alter physiological processes in turbot (Scophthalmus maximus), yet the molecular mechanisms driving these changes remain largely unclear. In this study, we applied a combined transcriptomic and metabolomic approach to reveal the systemic responses of turbot under thermal stress. Our results revealed that heat stress leads to significant alterations in gene expression and metabolite profiles in the liver. Key genes were found to be closely linked to amino acid metabolism, particularly those involved in leucine, isoleucine, and valine pathways—as well as the metabolism of specific compounds such as galactonic acid. Pathway analysis further identified critical roles for the PI3K-Akt signaling pathway, protein transport, and protein processing in the thermal stress response. These pathways are essential for maintaining cellular homeostasis, regulating energy balance, and ensuring proper protein function under stress conditions. The findings deepen our understanding of the molecular basis of heat adaptation in turbot and may inform strategies to improve thermotolerance in farmed fish, with potential implications for sustainable aquaculture under rising climate pressures.

Temperature has always been an important environmental factor, and changes in water temperature are closely related to the entire life process of fish. Investigating the impact of thermal stress on fish physiology is critical for optimizing aquaculture. This study employed transcriptomic and metabolomic approaches to investigate temperature-induced variations in the gene expression and metabolic profiles of turbot. The results showed that thermal stress could induce abnormal genes transcription, and functional annotation demonstrated predominant associations of these genes with key pathways including PI3K-Akt signaling, PPAR regulation, steroid biosynthesis, fatty acid metabolism, and FoxO signaling cascade. Metabolomic analysis revealed that amino acid metabolism was dysregulated, such as valine, leucine, and isoleucine. Joint analysis revealed significant positive associations between CDH1, Col9a1, and ECT2 genes and leucine/isoleucine metabolism. The expression levels of Plch2 and Col9a1 genes exhibited significant regulatory effects on valine metabolism. Moreover, the gene cluster comprising DNAJB6, Gcnt1 and trim71 was significantly involved in the metabolic regulation of galactonic acid. Collectively, these findings demonstrate that thermal stress induces significant alterations in gene expression, metabolic profiles, and signaling pathways in turbot, offering new perspectives for thermal stress mitigation strategies.