Cargando…

A low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the MafA gene in the offspring of Wistar rats

Maternal nutrition during gestation has important effects on gene expression-mediated metabolic programming in offspring. To evaluate the effect of a protein-restricted maternal diet during gestation, pancreatic islets from male progeny of Wistar rats were studied at postnatal days (PND) 36 (juvenil...

Descripción completa

Detalles Bibliográficos
Autores principales: Sosa-Larios, Tonantzin C., Ortega-Márquez, Ana L., Rodríguez-Aguilera, Jesús R., Vázquez-Martínez, Edgar R., Domínguez-López, Aaron, Morimoto, Sumiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040775/
https://www.ncbi.nlm.nih.gov/pubmed/36992977
http://dx.doi.org/10.3389/fvets.2023.1138564
_version_ 1784912554721542144
author Sosa-Larios, Tonantzin C.
Ortega-Márquez, Ana L.
Rodríguez-Aguilera, Jesús R.
Vázquez-Martínez, Edgar R.
Domínguez-López, Aaron
Morimoto, Sumiko
author_facet Sosa-Larios, Tonantzin C.
Ortega-Márquez, Ana L.
Rodríguez-Aguilera, Jesús R.
Vázquez-Martínez, Edgar R.
Domínguez-López, Aaron
Morimoto, Sumiko
author_sort Sosa-Larios, Tonantzin C.
collection PubMed
description Maternal nutrition during gestation has important effects on gene expression-mediated metabolic programming in offspring. To evaluate the effect of a protein-restricted maternal diet during gestation, pancreatic islets from male progeny of Wistar rats were studied at postnatal days (PND) 36 (juveniles) and 90 (young adults). The expression of key genes involved in β-cell function and the DNA methylation pattern of the regulatory regions of two such genes, Pdx1 (pancreatic and duodenal homeobox 1) and MafA (musculoaponeurotic fibrosarcoma oncogene family, protein A), were investigated. Gene expression analysis in the pancreatic islets of restricted offspring showed significant differences compared with the control group at PND 36 (P < 0.05). The insulin 1 and 2 (Ins1 and Ins2), Glut2 (glucose transporter 2), Pdx1, MafA, and Atf2 (activating transcription factor 2), genes were upregulated, while glucokinase (Gck) and NeuroD1 (neuronal differentiation 1) were downregulated. Additionally, we studied whether the gene expression differences in Pdx1 and MafA between control and restricted offspring were associated with differential DNA methylation status in their regulatory regions. A decrease in the DNA methylation levels was found in the 5' flanking region between nucleotides −8118 to −7750 of the MafA regulatory region in restricted offspring compared with control pancreatic islets. In conclusion, low protein availability during gestation causes the upregulation of MafA gene expression in pancreatic β-cells in the male juvenile offspring at least in part through DNA hypomethylation. This process may contribute to developmental dysregulation of β-cell function and influence the long-term health of the offspring.
format Online
Article
Text
id pubmed-10040775
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-100407752023-03-28 A low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the MafA gene in the offspring of Wistar rats Sosa-Larios, Tonantzin C. Ortega-Márquez, Ana L. Rodríguez-Aguilera, Jesús R. Vázquez-Martínez, Edgar R. Domínguez-López, Aaron Morimoto, Sumiko Front Vet Sci Veterinary Science Maternal nutrition during gestation has important effects on gene expression-mediated metabolic programming in offspring. To evaluate the effect of a protein-restricted maternal diet during gestation, pancreatic islets from male progeny of Wistar rats were studied at postnatal days (PND) 36 (juveniles) and 90 (young adults). The expression of key genes involved in β-cell function and the DNA methylation pattern of the regulatory regions of two such genes, Pdx1 (pancreatic and duodenal homeobox 1) and MafA (musculoaponeurotic fibrosarcoma oncogene family, protein A), were investigated. Gene expression analysis in the pancreatic islets of restricted offspring showed significant differences compared with the control group at PND 36 (P < 0.05). The insulin 1 and 2 (Ins1 and Ins2), Glut2 (glucose transporter 2), Pdx1, MafA, and Atf2 (activating transcription factor 2), genes were upregulated, while glucokinase (Gck) and NeuroD1 (neuronal differentiation 1) were downregulated. Additionally, we studied whether the gene expression differences in Pdx1 and MafA between control and restricted offspring were associated with differential DNA methylation status in their regulatory regions. A decrease in the DNA methylation levels was found in the 5' flanking region between nucleotides −8118 to −7750 of the MafA regulatory region in restricted offspring compared with control pancreatic islets. In conclusion, low protein availability during gestation causes the upregulation of MafA gene expression in pancreatic β-cells in the male juvenile offspring at least in part through DNA hypomethylation. This process may contribute to developmental dysregulation of β-cell function and influence the long-term health of the offspring. Frontiers Media S.A. 2023-03-13 /pmc/articles/PMC10040775/ /pubmed/36992977 http://dx.doi.org/10.3389/fvets.2023.1138564 Text en Copyright © 2023 Sosa-Larios, Ortega-Márquez, Rodríguez-Aguilera, Vázquez-Martínez, Domínguez-López and Morimoto. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Sosa-Larios, Tonantzin C.
Ortega-Márquez, Ana L.
Rodríguez-Aguilera, Jesús R.
Vázquez-Martínez, Edgar R.
Domínguez-López, Aaron
Morimoto, Sumiko
A low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the MafA gene in the offspring of Wistar rats
title A low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the MafA gene in the offspring of Wistar rats
title_full A low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the MafA gene in the offspring of Wistar rats
title_fullStr A low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the MafA gene in the offspring of Wistar rats
title_full_unstemmed A low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the MafA gene in the offspring of Wistar rats
title_short A low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the MafA gene in the offspring of Wistar rats
title_sort low-protein maternal diet during gestation affects the expression of key pancreatic β-cell genes and the methylation status of the regulatory region of the mafa gene in the offspring of wistar rats
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040775/
https://www.ncbi.nlm.nih.gov/pubmed/36992977
http://dx.doi.org/10.3389/fvets.2023.1138564
work_keys_str_mv AT sosalariostonantzinc alowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT ortegamarquezanal alowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT rodriguezaguilerajesusr alowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT vazquezmartinezedgarr alowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT dominguezlopezaaron alowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT morimotosumiko alowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT sosalariostonantzinc lowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT ortegamarquezanal lowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT rodriguezaguilerajesusr lowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT vazquezmartinezedgarr lowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT dominguezlopezaaron lowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats
AT morimotosumiko lowproteinmaternaldietduringgestationaffectstheexpressionofkeypancreaticbcellgenesandthemethylationstatusoftheregulatoryregionofthemafageneintheoffspringofwistarrats