Strain-Specific Liver Metabolite Profiles in Medaka

Abstract

The relationship between genetic variation and phenotypic traits is often poorly understood since specific genotypes do not always easily translate into associated phenotypes, especially for complex disorders. The genetic background has been shown to affect metabolic pathways and thus contribute to variations in the metabolome. Here, we tested the suitability of NMR metabolomics for comparative analysis of fish lines as a first step towards phenotype-genotype association studies. The Japanese rice fish, medaka (Oryzias latipes), is a widely used genetic vertebrate model with several isogenic inbred laboratory strains. We used liver extracts of medaka iCab and HO5 strains as a paradigm to test the feasibility of distinguishing the metabolome of two different inbred strains. Fifteen metabolites could be detected in uni- and multivariate analyses that showed strain-specific levels. Differences could be assigned to specific metabolic pathways. Our results show that NMR spectroscopy is a suitable method to detect variance of the metabolome caused by subtle genetic differences. Thus, it has the potential to address genotype–phenotype associations in medaka, providing an additional level of phenotypic analysis.

Medaka embryos as a model for metabolism of anabolic steroids

“…The liver as the main metabolizing organ is formed between day 2 and 4 of embryonic development (Iwamatsu 2004 ), but it is not known when the full metabolic capacity is established. Only recently, the adult metabolome of the medaka has been analyzed with respect to genomic variation in inbred strains (Soergel et al 2021 ). From our experiments with MD as only test substance, we propose to evaluate the metabolic capacity in embryos close before hatching that is day 8 of development at 26 °C.…”