A comparative metabolomic study of NHR‐49 in <i>Caenorhabditis elegans</i> and PPAR‐α in the mouse

Atherton, Helen; Jones, Oliver A.H.; Malik, Shahid M.; Miska, Eric A.; Griffin, Julian L.

doi:10.1016/j.febslet.2008.04.020

Cited by 63 publications

(55 citation statements)

References 16 publications

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“…This goal requires integrating metabolomic (Blaise et al 2007;Atherton et al 2008), proteomic (Dong et al 2007) and transcriptomic ( Jiang et al 2001) data. Studies of cellular growth in microbes are much more advanced than for any animal, and it is worth considering how our study compares to the various approaches that have been used in E. coli and yeast.…”

Section: Discussionmentioning

confidence: 99%

The cellular geometry of growth drives the amino acid economy ofCaenorhabditis elegans

et al. 2009

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The nematode Caenorhabditis elegans grows largely by increases in cell size. As a consequence of this, the surface: volume ratio of its cells must decline in the course of postembryonic growth. Here we use transcriptomic and metabolomic data to show that this change in geometry can explain a variety of phenomena during growth, including: (i) changes in the relative expression levels of cytoplasmic and membrane proteins; (ii) changes in the relative usage of the twenty amino acids in expressed proteins, as estimated by changes in the transcriptome; and (iii) changes in metabolite pools of free amino acids. We expect these relations to be universal in single cells and in whole multicellular organisms that grow largely by increases in cell size, but not those that grow by cell proliferation.

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Section: Discussionmentioning

confidence: 99%

The cellular geometry of growth drives the amino acid economy ofCaenorhabditis elegans

et al. 2009

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“…Metabolomics in particular has several advantages in this respect. It is quick and cheap on a per sample basis and, unlike proteomics and transcriptomics (which require some prior knowledge of the respective protein and DNA sequences), the vast majority of metabolites are common across a range of taxa and have the same chemical structure regardless of the organism from which they are extracted (Atherton et al 2008). Metabolite concentrations are also known to be sensitive to physiological and developmental states, meaning that metabolomics can be used to detect subtle differences in phenotypic responses to a given stimulus .…”

Section: Introductionmentioning

confidence: 99%

A metabolomics based test of independent action and concentration addition using the earthworm Lumbricus rubellus

et al. 2012

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A major challenge in ecotoxicology is to understand the effects of multiple toxicants on organisms. Here we assess the effects on survival, weight change, cocoon production and metabolism caused by exposure to two similarly acting (imidacloprid/thiacloprid) and two dissimilarly acting (chlorpyrifos/Nickel) chemicals on the earthworm Lumbricus rubellus. We assessed the standard models of concentration addition (CA) and independent action (IA), in conjunction with a metabolomics based approach to elucidate mechanisms of effect. For imidacloprid and thiacloprid the reproductive effects indicated probable additivity. Although this suggests joint effects through a similar mechanism, metabolite changes for each pesticide actually indicated distinct effects. Further, earthworms exposed to a 0.5 toxic unit equitoxic mixture demonstrated metabolic effects intermediate between those for each pesticide, indicating a non-interactive, independent joint effect. For higher effect level mixtures (1 and 1.5 toxic units), metabolite changes associated with thiacloprid exposure began to dominate. The metabolomic effects of the two dissimilarly acting chemicals were distinct, confirming separate modes of action and both proved more toxic than anticipated from previous studies. In the mixtures, phenotypic effects were in accordance with IA estimates, while metabolite changes were dominated by Ni effects, even though chlorpyrifos contributed most to reproductive toxicity. This could be attributed to the greater systematic effect of Ni when compared to the more specifically acting chlorpyrifos.

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“…NHR-49 in C. elegans has been shown to be the human homolog of peroxisome proliferator-activated receptor-a (PPARa). 15 C. elegans regulation of feeding The C. elegans model has been used to show the effect of calorie restriction for increasing lifespan. Pharyngeal movements enable C. elegans to pump food into its body and feed.…”

Section: Introductionmentioning

confidence: 99%

Caenorhabditis elegans as a model for obesity research

Zheng

Greenway

2011

Int J Obes

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Caenorhabditis elegans (C. elegans) is a small nematode that conserves 65% of the genes associated with human disease, has a 21-day lifespan, reproductive cycles of 3 days, large brood sizes, lives in an agar dish and does not require committee approvals for experimentation. Research using C. elegans is encouraged and a Caenorhabditis Genetics Center (CGC, Minnesota) is funded by the National Institutes of Health-National Center for Research Resources. Many genetically manipulated strains of C. elegans are available at nominal cost from the CGC. Studies using the C. elegans model have explored insulin signaling, response to dietary glucose, the influence of serotonin on obesity, satiety, feeding and hypoxia-associated illnesses. C. elegans has also been used as a model to evaluate potential obesity therapeutics, explore the mechanisms behind single gene mutations related to obesity and to define the mechanistic details of fat metabolism. Obesity now affects a third of the US population and is becoming a progressively more expensive public health problem. Faster and less expensive methods to reach more effective treatments are clearly needed. We present this review hoping to stimulate interest in using the C. elegans model as a vehicle to advance the understanding and future treatment of obesity.

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A comparative metabolomic study of NHR‐49 in Caenorhabditis elegans and PPAR‐α in the mouse

Cited by 63 publications

References 16 publications

The cellular geometry of growth drives the amino acid economy ofCaenorhabditis elegans

The cellular geometry of growth drives the amino acid economy ofCaenorhabditis elegans

A metabolomics based test of independent action and concentration addition using the earthworm Lumbricus rubellus

Caenorhabditis elegans as a model for obesity research

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