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The importance of sulfur-containing metabolites in discriminating fecal extracts between normal and type 2 diabetic mice.
J. Proteome Res. 13, 4220-4231 (2014)
A metabolic disorder such as Type 2 Diabetes mellitus (T2DM) is a complex disease induced by genetic, environmental and nutritional factors. The db/db mouse model, bearing a non-functional leptin receptor is widely used to investigate the pathophysiology of T2DM. Fecal extracts of db/db and wild type littermates were studied to unravel a broad spectrum of new and relevant metabolites related to T2DM as proxies of the interplay of gut microbiome and murine metabolomes. The non-targeted metabolomics approach consists of an integrated analytical concept of high-resolution mass spectrometry FT-ICR-MS followed by UPLC-TOF-MS/MS experiments. We demonstrate that a metabolic disorder such as T2DM affects the gastrointestinal tract environment thereby influencing different metabolic pathways and their respective metabolites in diabetic mice. Fatty acids, bile acids concerning cholic and deoxycholic acid and steroid metabolism were highly discriminative comparing fecal metabolomes of wt and db/db mice. Furthermore, sulfur-(S)-containing metabolites including N-acyl taurines were altered in diabetic mice, enabling to focus on S-containing metabolites, especially the sulfate and taurine conjugates of bile and fatty acids. Different sulfate containing bile acids including sulfocholic acid, oxocholic acid sulfate, taurocholic acid sulfate and cyprinol sulfate were significantly altered in diabetic mice. Moreover, we identified twelve new sulfate and taurine conjugates of hydroxylated fatty acids with significant importance in T2DM metabolism in db/db mice.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Type 2 Diabetes, db/db mice, metabolomics, high-resolution mass spectrometry,
meta-metabolome, sulfur-containing metabolites, FT-ICR-MS; Chromatography-mass Spectrometry; N-acyl Taurines; Db/db Mice; Metabolomics Data; Mutant Mice; Mouse; Bile; Rat; Plasma; Urine
Language
english
Publication Year
2014
HGF-reported in Year
2014
ISSN (print) / ISBN
1535-3893
e-ISSN
1535-3907
Journal
Journal of Proteome Research
Quellenangaben
Volume: 13,
Issue: 10,
Pages: 4220-4231
Publisher
American Chemical Society (ACS)
Publishing Place
Washington
Reviewing status
Peer reviewed
Institute(s)
Research Unit BioGeoChemistry and Analytics (BGC)
Research Unit Microbe-Plant Interactions (AMP)
Institute of Experimental Genetics (IEG)
Research Unit Microbe-Plant Interactions (AMP)
Institute of Experimental Genetics (IEG)
POF-Topic(s)
30202 - Environmental Health
20402 - Sustainable Plant Production
30201 - Metabolic Health
90000 - German Center for Diabetes Research
20402 - Sustainable Plant Production
30201 - Metabolic Health
90000 - German Center for Diabetes Research
Research field(s)
Environmental Sciences
Genetics and Epidemiology
Genetics and Epidemiology
PSP Element(s)
G-504800-001
G-504600-001
G-500600-003
G-500600-001
G-501900-062
G-504600-001
G-500600-003
G-500600-001
G-501900-062
PubMed ID
24991707
WOS ID
WOS:000342719200002
Scopus ID
84907810821
Erfassungsdatum
2014-07-08