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Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice

There is accumulating evidence for fetal programming of later kidney disease by maternal obesity or associated conditions. We performed a hypothesis-generating study to identify potentially underlying mechanisms. Female mice were randomly split in two groups and fed either a standard diet (SD) or hi...

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Autores principales: Nüsken, Eva, Turnwald, Eva-Maria, Fink, Gregor, Voggel, Jenny, Yosy, Christopher, Kretschmer, Tobias, Handwerk, Marion, Wohlfarth, Maria, Weber, Lutz T., Hucklenbruch-Rother, Eva, Dötsch, Jörg, Nüsken, Kai-Dietrich, Appel, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571731/
https://www.ncbi.nlm.nih.gov/pubmed/31083566
http://dx.doi.org/10.3390/jcm8050663
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author Nüsken, Eva
Turnwald, Eva-Maria
Fink, Gregor
Voggel, Jenny
Yosy, Christopher
Kretschmer, Tobias
Handwerk, Marion
Wohlfarth, Maria
Weber, Lutz T.
Hucklenbruch-Rother, Eva
Dötsch, Jörg
Nüsken, Kai-Dietrich
Appel, Sarah
author_facet Nüsken, Eva
Turnwald, Eva-Maria
Fink, Gregor
Voggel, Jenny
Yosy, Christopher
Kretschmer, Tobias
Handwerk, Marion
Wohlfarth, Maria
Weber, Lutz T.
Hucklenbruch-Rother, Eva
Dötsch, Jörg
Nüsken, Kai-Dietrich
Appel, Sarah
author_sort Nüsken, Eva
collection PubMed
description There is accumulating evidence for fetal programming of later kidney disease by maternal obesity or associated conditions. We performed a hypothesis-generating study to identify potentially underlying mechanisms. Female mice were randomly split in two groups and fed either a standard diet (SD) or high fat diet (HFD) from weaning until mating and during pregnancy. Half of the dams from both groups were treated with metformin ((M), 380 mg/kg), resulting in four experimental groups (SD, SD-M, HFD, HFD-M). Caesarean section was performed on gestational day 18.5. Fetal kidney tissue was isolated from cryo-slices using laser microdissection methods and a proteomic screen was performed. For single proteins, a fold change ≥1.5 and q-value <0.05 were considered to be statistically significant. Interestingly, HFD versus SD had a larger effect on the proteome of fetal kidneys (56 proteins affected; interaction clusters shown for proteins concerning transcription/translation, mitochondrial processes, eicosanoid metabolism, H2S-synthesis and membrane remodeling) than metformin exposure in either SD (29 proteins affected; clusters shown for proteins involved in transcription/translation) or HFD (6 proteins affected; no cluster). By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet.
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spelling pubmed-65717312019-06-18 Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice Nüsken, Eva Turnwald, Eva-Maria Fink, Gregor Voggel, Jenny Yosy, Christopher Kretschmer, Tobias Handwerk, Marion Wohlfarth, Maria Weber, Lutz T. Hucklenbruch-Rother, Eva Dötsch, Jörg Nüsken, Kai-Dietrich Appel, Sarah J Clin Med Article There is accumulating evidence for fetal programming of later kidney disease by maternal obesity or associated conditions. We performed a hypothesis-generating study to identify potentially underlying mechanisms. Female mice were randomly split in two groups and fed either a standard diet (SD) or high fat diet (HFD) from weaning until mating and during pregnancy. Half of the dams from both groups were treated with metformin ((M), 380 mg/kg), resulting in four experimental groups (SD, SD-M, HFD, HFD-M). Caesarean section was performed on gestational day 18.5. Fetal kidney tissue was isolated from cryo-slices using laser microdissection methods and a proteomic screen was performed. For single proteins, a fold change ≥1.5 and q-value <0.05 were considered to be statistically significant. Interestingly, HFD versus SD had a larger effect on the proteome of fetal kidneys (56 proteins affected; interaction clusters shown for proteins concerning transcription/translation, mitochondrial processes, eicosanoid metabolism, H2S-synthesis and membrane remodeling) than metformin exposure in either SD (29 proteins affected; clusters shown for proteins involved in transcription/translation) or HFD (6 proteins affected; no cluster). By further analysis, ATP6V1G1, THY1, PRKCA and NDUFB3 were identified as the most promising candidates potentially mediating reprogramming effects of metformin in a maternal high fat diet. MDPI 2019-05-11 /pmc/articles/PMC6571731/ /pubmed/31083566 http://dx.doi.org/10.3390/jcm8050663 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nüsken, Eva
Turnwald, Eva-Maria
Fink, Gregor
Voggel, Jenny
Yosy, Christopher
Kretschmer, Tobias
Handwerk, Marion
Wohlfarth, Maria
Weber, Lutz T.
Hucklenbruch-Rother, Eva
Dötsch, Jörg
Nüsken, Kai-Dietrich
Appel, Sarah
Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice
title Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice
title_full Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice
title_fullStr Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice
title_full_unstemmed Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice
title_short Maternal High Fat Diet and in-Utero Metformin Exposure Significantly Impact upon the Fetal Renal Proteome of Male Mice
title_sort maternal high fat diet and in-utero metformin exposure significantly impact upon the fetal renal proteome of male mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571731/
https://www.ncbi.nlm.nih.gov/pubmed/31083566
http://dx.doi.org/10.3390/jcm8050663
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