Metabolic Profiling of Multiorgan Samples: Evaluation of MODY5/RCAD Mutant Mice

Frida Torell; Kate Bennet; Silvia Cereghini; Melanie Fabre; Stefan Rannar; Katrin Lundstedt-Enkel; Thomas Moritz; Cecile Haumaitre; Johan Trygg; Torbjorn Lundstedt

doi:10.1021/acs.jproteome.7b00821

Metabolic Profiling of Multiorgan Samples: Evaluation of MODY5/RCAD Mutant Mice

Frida Torell, Kate Bennet, Silvia Cereghini, Melanie Fabre, Stefan Rannar, Katrin Lundstedt-Enkel, Thomas Moritz, Cecile Haumaitre, Johan Trygg, Torbjorn Lundstedt

2 Citations (Scopus)

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.

Original language	Undefined/Unknown
Journal	Journal of Proteome Research
Volume	17
Issue number	7
Pages (from-to)	2293-2306
Number of pages	14
ISSN	1535-3893
DOIs	https://doi.org/10.1021/acs.jproteome.7b00821
Publication status	Published - 6 Jul 2018
Externally published	Yes

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10.1021/acs.jproteome.7b00821

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title = "Metabolic Profiling of Multiorgan Samples: Evaluation of MODY5/RCAD Mutant Mice",

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.",

author = "Frida Torell and Kate Bennet and Silvia Cereghini and Melanie Fabre and Stefan Rannar and Katrin Lundstedt-Enkel and Thomas Moritz and Cecile Haumaitre and Johan Trygg and Torbjorn Lundstedt",

year = "2018",

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doi = "10.1021/acs.jproteome.7b00821",

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T1 - Metabolic Profiling of Multiorgan Samples: Evaluation of MODY5/RCAD Mutant Mice

AU - Torell, Frida

AU - Bennet, Kate

AU - Cereghini, Silvia

AU - Fabre, Melanie

AU - Rannar, Stefan

AU - Lundstedt-Enkel, Katrin

AU - Moritz, Thomas

AU - Haumaitre, Cecile

AU - Trygg, Johan

AU - Lundstedt, Torbjorn

PY - 2018/7/6

Y1 - 2018/7/6

N2 - 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.

AB - 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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