Metabolomics – A Tool for Grouping
of Chemicals and Illustration of
Mechanism of Action
By Kasper Skov
Agenda
• Introduction
– Metabolism and metabolomics
– Mass spectrometry
– Statistics
• Results
– Influence of Perfluorononanoic acid
(PFNA) ± mixture of EDC on rat
blood metabolome
• Conclusion
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Metabolomics
• Analysis of all (or as many as possible) low molecular weight metabolites
in a specific biological compartment. In the present study rat blood.
Metabolism
Metabolomics is the scientific study of chemical processes involving metabolites.
Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that
specific cellular processes leave behind", the study of their small-molecule metabolite
profiles.
The metabolome represents the collection of all metabolites in a biological cell, tissue, organ
or organism, which are the end products of cellular processes.
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Wikipedia
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Compounds in the metabolome, examples
Amino acids
cholesterol
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carbohydrates
Fatty acids
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Metabolomics - relation to other omics
• Analysis of the metabolism [omics = analysis of ; metabol = metabolism]
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Mass spectrometry
343.123488
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Analysis
one chromatogram
from each animal
m/z
1000
800
600
400
200
0
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2
4
6
8
10
Time [min]
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Statistics – a tool for identification
Comparison of exposed vs non-exposed animals
PC 2
0.50
0.25
0.00
Animaldata
-0.25
-0.50
-0.4
0.0
0.4
PC 1
Scoreplot
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Design of rat study
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Metabolomics – workflow
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Results
PFNA
Experiment
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Low dose effect
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Phospholipids
Cocktail effect?
Or similar
composition
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Mechanisms of action for PFNA
• Decreased plasma lipid levels
• Activation of Peroxisome proliferator-activated
receptor (PPAR)
• Two possible MoA
– PPAR is activated => increased beta-oxidation,
explaining the decreased levels of plasma lipids
– The plasma lipid concentration is lower due to a
response to achieve more energy to protect the
body
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Metabolomics
Conclusion and future perspective
• We identified changes in the metabolism even at
low dose exposure
• Study how exogenous compounds effect the body
metabolome.
• With a larger database of toxicity studies with
metabolomic investigation. Grouping of chemicals
which similar mechanism of action based on
similar changes in metabolite panels.
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Thanks to
• The cocktail team.
• Danish Veterinary and Food Administration
• Ministry of Food, Agriculture and Fisheries
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Questions
?
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