A Great Catch for Investigating Inborn Errors of Metabolism—Insights Obtained from Zebrafish

Abstract

Inborn errors of metabolism cause abnormal synthesis, recycling, or breakdown of amino acids, neurotransmitters, and other various metabolites. This aberrant homeostasis commonly causes the accumulation of toxic compounds or depletion of vital metabolites, which has detrimental consequences for the patients. Efficient and rapid intervention is often key to survival. Therefore, it requires useful animal models to understand the pathomechanisms and identify promising therapeutic drug targets. Zebrafish are an effective tool to investigate developmental mechanisms and understanding the pathophysiology of disorders. In the past decades, zebrafish have proven their efficiency for studying genetic disorders owing to the high degree of conservation between human and zebrafish genes. Subsequently, several rare inherited metabolic disorders have been successfully investigated in zebrafish revealing underlying mechanisms and identifying novel therapeutic targets, including methylmalonic acidemia, Gaucher’s disease, maple urine disorder, hyperammonemia, TRAPPC11-CDGs, and others. This review summarizes the recent impact zebrafish have made in the field of inborn errors of metabolism.

In silico biomarker analysis of the adverse effects of perfluorooctane sulfonate (PFOS) exposure on the metabolic physiology of embryo-larval zebrafish

“…The high level of genomic orthology and biochemical conservation between zebrafish and humans ensures relevance to the predictions of adverse effects in humans (Howe et al, 2013;Breuer and Patten, 2020). And conservation of zebrafish endocrinology and biochemistry with other piscine species also makes it an effective model system to study other aquatic wildlife (Hutchinson et al, 2003;Busby et al, 2010).…”

“…The in silico approach taken in this manuscript involved integrating metabolomics and transcriptomics (RNA sequencing) datasets from in vivo toxicological studies, generated by other authors, in which embryo-larval life-stages of zebrafish were exposed to PFOS (Ortiz-Villanueva et al, 2018;Martínez et al, 2019). Zebrafish were chosen as a model organism due to their common use as an in vivo model for aquatic wildlife and human health (Hutchinson et al, 2003;Tanguay, 2018;Breuer and Patten, 2020). Untargeted metabolomics (Ortiz-Villanueva et al, 2018) and transcriptomics datasets (Martínez et al, 2019) from 5 days post fertilized (dpf) embryo-larval zebrafish exposed to PFOS (from 2 -5 dpf) were used for model parameterization.…”

Omics-Based Approaches for the Characterization of Pompe Disease Metabolic Phenotypes

“…Also, the application of computational-based data augmentation techniques to create synthetic sets of samples that have proven to be an adequate strategy to overcome the limited number of samples often found in other LSDs datasets [ 147 ] could be of interest in PD studies. A significant number of more close-to-patients models have been developed in recent years [ 148 , 149 , 150 ]. The information derived from the metabolomic study of these models could have important implications for assessing these differences and for improving drug targeting and clinical efficacy of PD therapies that are currently under development.…”

Synthesis and application of visual AIE fluorescent probe for lipid droplets in vivo

“…Given the selective LDs imaging of CMDP derivatives, we chose zebrafish as the experimental model to explore CMDP derivatives' imaging capability in vivo. Three days after fertilization, the yolk sac has lots of neutral lipids that provides energy for zebrafish larval growth, seeing it is an ideal model for researching the lipid-associated diseases [22][23][24][25]. The zebrafish were observed after incubated with CMDP-CN and CMDP-NO2 for 15 mins and were imaged rapidly via CLSM.…”