Session: Session 5

A multimodal study using mass spectrometry imaging to explore age-related metabolic changes in a fish model

Aurore MALO^1,2, Léana PORCHER-BIBES^1,2, Yannick JEANSON¹, Hanna KULYK², Claire DUPONT¹, Guillaume MARTI², Jean-Philippe PRADÈRE¹, Spiro KHOURY^1,2, Jean-Charles PORTAIS^1,2

¹RESTORE, University of Toulouse, Inserm U1031, CNRS 5070, UPS, EFS. 4bis avenue Hubert Curien 31100 Toulouse, France, TOULOUSE, France
²MetaboHUB-MetaToul, National Infrastructure of Metabolomics and Fluxomics, Toulouse, 31077, France, TOULOUSE, France

Introduction

Zebrafish is a valuable model in aging research due to their metabolic and genetic similarity to humans. This study aims to investigate the metabolic profile of zebrafish at different ages through an integrated metabolomics approach using mass spectrometry imaging (MSI) and HPLC-HRMS in order to understand the metabolic alterations associated with age-related diseases.

Methodology

Zebrafish samples were collected at different stages of development. Thin slices were prepared and analyzed in their native state without extensive sample preparation using DESI-MSI. Metabolic imaging was associated with histological, microscopic and HPLC-HRMS/MS analyses to provide an in-depth exploration of zebrafish metabolic profiles.

Results

Our multimodal approach revealed distinct metabolic profiles in the different tissues and developmental stages of zebrafish. DESI-MSI revealed specific spatial distributions of amino acids, organic acids, lipids, and other small molecules in the different tissues. Histological and microscopic studies allowed to correlate the spatial distribution of metabolites with tissue structure. HPLC-HRMS/MS experiments confirmed the structure of the metabolites annotated by MSI. Comparative analyses between young and old zebrafish highlighted significant alterations in key metabolic pathways, especially those related to energy metabolism. The taurine was found to be more abundant in old zebrafish, while lactate, glucose, glycerol-3-phosphate and some amino acids were more abundant in the young animals. The metabolic profile of the embryos was also studied and showed differences in abundance compared to adult zebrafish.

Conclusion

This study demonstrated the efficiency of DESI-MSI in mapping the whole-organism metabolome of zebrafish. The multimodal approach enabled the identification of age-related changes in metabolic pathways, particularly in energy metabolism, providing potential biomarkers for further investigation.