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Abstract

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.

Keywords

HNF1B-associated diseases; metabolomics; OPLS-DA; multiorgan samples; MODY5; RCAD; mouse model

Published in

Journal of Proteome Research
2018, volume: 17, number: 7, pages: 2293-2306
Publisher: AMER CHEMICAL SOC

SLU Authors

UKÄ Subject classification

Bioinformatics and Computational Biology (Methods development to be 10203)

Publication identifier

  • DOI: https://doi.org/10.1021/acs.jproteome.7b00821

Permanent link to this page (URI)

https://res.slu.se/id/publ/96388