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Metabolic Profiling of Multiorgan Samples: Evaluation of MODY5/RCAD Mutant Mice
Karlsruhe Inst Technol, Accelerator Lab ACL, D-76344 Karlsruhe, Germany; Umeå Univ, Dept Chem, Computat Life Sci Cluster CLiC, S-90187 Umeå, Sweden.
AcureOmics AB, S-90736 Umeå, Sweden.
CNRS, UMR7622, Paris, France; UPMC, Sorbonne Univ, UMR7622, Paris, France; INSERM, U 1156, Paris, France.
CNRS, UMR7622, F-75005 Paris, France; UPMC, Sorbonne Univ, UMR7622, F-75005 Paris, France; INSERM, U 1156, Paris, France.
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2018 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 17, no 7, p. 2293-2306Article in journal (Refereed) Published
Abstract [en]

In the present study, we performed a metabolomics analysis to evaluate a MODY5/RCAD mouse mutant line as a potential model for HNF1B-associated diseases. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) of gut, kidney, liver, muscle, pancreas, and plasma samples uncovered the tissue specific metabolite distribution. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to identify the differences between MODY5/RCAD and wild-type mice in each of the tissues. The differences included, for example, increased levels of amino acids in the kidneys and reduced levels of fatty acids in the muscles of the MODY5/RCAD mice. Interestingly, campesterol was found in higher concentrations in the MODY5/RCAD mice, with a four-fold and three-fold increase in kidneys and pancreas, respectively. As expected, the MODY5/RCAD mice displayed signs of impaired renal function in addition to disturbed liver lipid metabolism, with increased lipid and fatty acid accumulation in the liver. From a metabolomics perspective, the MODY5/RCAD model was proven to display a metabolic pattern similar to what would be suspected in HNF1B-associated diseases. These findings were in line with the presumed outcome of the mutation based on the different anatomy and function of the tissues as well as the effect of the mutation on development.

Place, publisher, year, edition, pages
2018. Vol. 17, no 7, p. 2293-2306
Keywords [en]
HNF1B-associated diseases, metabolomics, OPLS-DA, multiorgan samples, MODY5, RCAD, mouse model
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-361549DOI: 10.1021/acs.jproteome.7b00821ISI: 000438469900004PubMedID: 29873499OAI: oai:DiVA.org:uu-361549DiVA, id: diva2:1254022
Funder
Swedish Research Council, 2011-6044Swedish Research Council, 2016-04376EU, FP7, Seventh Framework ProgrammeAvailable from: 2018-10-08 Created: 2018-10-08 Last updated: 2018-10-08Bibliographically approved

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Lundstedt-Enkel, KatrinLundstedt, Torbjörn

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