The Time Is Right to Focus on Model Organism Metabolomes

Edison, Arthur S.; Hall, Robert D.; Junot, Christophe; Karp, Peter D.; Kurland, Irwin J.; Mistrik, Robert; Reed, Laura K.; Saito, Kazuki; Salek, Reza M.; Steinbeck, Christoph; Sumner, Lloyd W.; Viant, Mark R.

doi:10.3390/metabo6010008

Cited by 65 publications

(48 citation statements)

References 28 publications

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“…60 Furthermore, the emerging field of metabolomics has made its way into zebrafish and will further contribute in bridging the gap between genotype and phenotype and from bench to bedside. 61,62 Goby, tilapia and perch Some other non-traditional fish models have also been tested as models for diabetes, and in some cases the work precedes the work using zebrafish. For example, one of the first fish models for T1D was the goby Gillichthys mirabilis (Fig.…”

Section: Future Of Zebrafish In Metabolic Disease Researchmentioning

confidence: 99%

Sweet fish: Fish models for the study of hyperglycemia and diabetes

Krishnan

Rohner

2018

Journal of Diabetes

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Fish are good for your health in more ways than you may expect. For one, eating fish is a common dietary recommendation for a healthy diet. However, fish have much more to provide than omega-3 fatty acids to your circulatory system. Some fish species now serve as important and innovative model systems for diabetes research, providing novel and unique advantages compared with classical research models. Not surprisingly, the largest share of diabetes research in fish occurs in the laboratory workhorse among fish, the zebrafish (Danio rerio). Established as a genetic model system to study development, these small cyprinid fish have eventually conquered almost every scientific discipline and, over the past decade, have emerged as an important model system for metabolic diseases, including diabetes mellitus. In this review we highlight the practicability of using zebrafish to study diabetes and hyperglycemia, and summarize some of the recent research and breakthroughs made using this model. Equally exciting is the appearance of another emerging discipline, one that is taking advantage of evolution by studying cases of naturally occurring insulin resistance in fish species. We briefly discuss two such models in this review, namely the rainbow trout (Oncorhynchus mykiss) and the cavefish (Astyanax mexicanus). Highlights• Different fish species are becoming increasingly attractive as models for the study of hyperglycemia and diabetes due to the ease of generating and maintaining large numbers of animals. • Some fish species exhibit unique physiological and evolutionary features that could be used to gain further insights into vertebrate glucose homeostasis and dysregulation.

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Section: Future Of Zebrafish In Metabolic Disease Researchmentioning

confidence: 99%

Sweet fish: Fish models for the study of hyperglycemia and diabetes

Krishnan

Rohner

2018

Journal of Diabetes

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“…Reconstruction of genome-scale metabolic networks (GSMs) is a useful and powerful way to integrate data about the metabolism of model organisms due to the increasing availability of genome data [1]. In parallel, metabolomics has maturated as a separate research field, and both are now converging, with the proposal to focus on model organism metabolomes [2].…”

Section: Introductionmentioning

confidence: 99%

Inferring biochemical reactions and metabolite structures to cope with metabolic pathway drift

Belcour

Girard

Aïte

et al. 2018

Preprint

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Inferring genome-scale metabolic networks in emerging model organisms is challenging because of incomplete biochemical knowledge and incomplete conservation of biochemical pathways during evolution. This limits the possibility to automatically transfer knowledge from well-established model organisms. Therefore, specific bioinformatic tools are necessary to infer new biochemical reactions and new metabolic structures that can be checked experimentally. Using an integrative approach combining both genomic and metabolomic data in the red algal model Chondrus crispus, we show that, even metabolic pathways considered as conserved, like sterol or mycosporine-like amino acids (MAA) synthesis pathways, undergo substantial turnover. This phenomenon, which we formally define as "metabolic pathway drift", is consistent with findings from other areas of evolutionary biology, indicating that a given phenotype can be conserved even if the underlying molecular mechanisms are changing. We present a proof of concept with a new methodological approach to formalize the logical reasoning necessary to infer new reactions and new molecular structures, based on previous biochemical knowledge. We use this approach to infer previously unknown reactions in the sterol and MAA pathways. Author summaryGenome-scale metabolic models describe our current understanding of all metabolic pathways occuring in a given organism. For emerging model species, where few biochemical data are available about really occurring enzymatic activities, such metabolic models are mainly based on transferring knowledge from other more studied species, based on the assumption that the same genes have the same function in the compared species. However, integration of metabolomic data into genome-scale metabolic models leads to situations where gaps in pathways cannot be filled by known enzymatic reactions from existing databases. This is due to structural variation in metabolic pathways accross evolutionary time. In such cases, it is necessary to use complementary approaches to infer new reactions and new metabolic intermediates using logical reasoning, based on available partial biochemical knowledge.Here we present a proof of concept that this is feasible and leads to hypotheses that are precise enough to be a starting point for new experimental work. the well-studied human pathogenic bacterium Mycobacterium tuberculosis, high throughput metabolomic screens revealed an unexpected diversity of reactions in central carbon metabolism [9]. Evolutionary models have already been developed to explain the arising of new pathways, with most experimental validations being focused so far at the level of individual enzyme activities [10]. The complementary question, how much conserved corresponding to Z-palythenic acid in C. crispus extracts, which does not support dehydration occuring before decarboxylation, as proposed in other species (Fig 4 and [65]). The structure of a new intermediate was therefore inferred manually, leading to MAA2 on Figure 8.Calculating its m/z ratio,...

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“…Here, we first summarize the basics of genome-scale metabolic network modeling, and then explore GSMNMs and their applications in common model organisms [3] (Figure 1). GSMNMs mentioned are listed in Table 1, together with the latest human model [4*] for comparison.…”

Section: Introductionmentioning

confidence: 99%

Metabolic network modeling with model organisms

Yılmaz

Walhout

2017

Current Opinion in Chemical Biology

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Flux balance analysis (FBA) with genome-scale metabolic network models (GSMNM) allows systems level predictions of metabolism in a variety of organisms. Different types of predictions with different accuracy levels can be made depending on the applied experimental constraints ranging from measurement of exchange fluxes to the integration of gene expression data. Metabolic network modeling with model organisms has pioneered method development in this field. In addition, model organism GSMNMs are useful for basic understanding of metabolism, and in the case of animal models, for the study of metabolic human diseases. Here, we discuss GSMNMs of most highly used model organisms with the emphasis on recent reconstructions.

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The Time Is Right to Focus on Model Organism Metabolomes

Cited by 65 publications

References 28 publications

Sweet fish: Fish models for the study of hyperglycemia and diabetes

Sweet fish: Fish models for the study of hyperglycemia and diabetes

Inferring biochemical reactions and metabolite structures to cope with metabolic pathway drift

Metabolic network modeling with model organisms

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