Metabolomics is a systems approach to studying the small, endogenous metabolites in an organ, biofluid or whole organism. It can be used as a screening tool for metabolite profiling, or to detect changes in the metabolome brought on by external or internal stressors. The purpose of this review is to summarize and evaluate the information obtained from the application of metabolomics in fish research and to discuss its future potential. It is already clear that metabolomics has contributed new knowledge about fish in areas such as basic physiology and development, disease, water pollution and aspects concerning fish as foodstuffs.

The protonmotive force (Δp) across the mitochondrial inner membrane drives ATP synthesis. In addition, the energy stored in Δp can be dissipated by proton leak through the inner membrane, contributing to basal metabolic rate and thermogenesis. Increasing mitochondrial proton leak pharmacologically should decrease the efficiency of oxidative phosphorylation and counteract obesity by enabling fatty acids to be oxidised with decreased ATP production. While protonophores such as 2,4-dinitrophenol (DNP) increase mitochondrial proton leak and have been used to treat obesity, a slight increase in DNP concentration above the therapeutically effective dose disrupts mitochondrial function and leads to toxicity. Therefore we set out to develop a less toxic protonophore that would increase proton leak significantly at high Δp but not at low Δp. Our design concept for a potential self-limiting protonophore was to couple the DNP moiety to the lipophilic triphenylphosphonium (TPP) cation and this was achieved by the preparation of 3-(3,5-dinitro-4-hydroxyphenyl)propyltriphenylphosphonium methanesulfonate (MitoDNP). TPP cations accumulate within mitochondria driven by the membrane potential (Δψ), the predominant component of Δp. Our hypothesis was that MitoDNP would accumulate in mitochondria at high Δψ where it would act as a protonophore, but that at lower Δψ the accumulation and uncoupling would be far less. We found that MitoDNP was extensively taken into mitochondria driven by Δψ. However MitoDNP did not uncouple mitochondria as judged by its inability to either increase respiration rate or decrease Δψ. Therefore MitoDNP did not act as a protonophore, probably because the efflux of deprotonated MitoDNP was inhibited.

The aim of this study was to evaluate whether NMR-based metabolomics is a suitable method to generate an integrated view on metabolic processes during food deprivation in salmonid fish. Juvenile rainbow trout ( Oncorhynchus mykiss ) weighing 43–115 g were either fed ad libitum or deprived of food for 28 days at 10°C to investigate catabolic effects on energy reserves and metabolite patterns. The NMR analysis of plasma, liver, and muscle extracts revealed significant fasting-induced changes in the metabolome. Altered plasma lipoprotein levels and tissue-specific patterns of fatty acid mobilization were the most prominent responses, emphasizing the role of lipids as the primary energy source during fasting. In plasma, very-low-density lipoprotein levels increased in food-deprived fish compared with fed fish, whereas levels of high-density lipoprotein decreased. Signs of muscle protein catabolism were also observed as changes in the alanine dynamics. The results further suggest that mechanisms to preserve liver glycogen are present in the food-deprived fish. This study thus demonstrates the utility of NMR-based metabolomics of tissue extracts and plasma to describe the integrated metabolic status of fish.