Metabolic Profiling of Multiorgan Samples: Evaluation of MODY5/RCAD Mutant Mice.
J Proteome Res
; 17(7): 2293-2306, 2018 07 06.
Article
em En
| MEDLINE
| ID: mdl-29873499
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Modelos Animais de Doenças
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Metabolômica
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Camundongos Mutantes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article