Cargando…

Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring

Exposure to adverse early-life environments (AME) increases the incidence of developing adult-onset non-alcoholic fatty liver disease (NAFLD). DNA methylation has been postulated to link AME and late-onset diseases. This study aimed to investigate whether and to what extent the hepatic DNA methylome...

Descripción completa

Detalles Bibliográficos
Autores principales: Fu, Qi, Cheung, Warren A., Majnik, Amber V., Ke, Xingrao, Pastinen, Tomi, Lane, Robert H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180730/
https://www.ncbi.nlm.nih.gov/pubmed/37432267
http://dx.doi.org/10.3390/nu15092167
_version_ 1785041404743909376
author Fu, Qi
Cheung, Warren A.
Majnik, Amber V.
Ke, Xingrao
Pastinen, Tomi
Lane, Robert H.
author_facet Fu, Qi
Cheung, Warren A.
Majnik, Amber V.
Ke, Xingrao
Pastinen, Tomi
Lane, Robert H.
author_sort Fu, Qi
collection PubMed
description Exposure to adverse early-life environments (AME) increases the incidence of developing adult-onset non-alcoholic fatty liver disease (NAFLD). DNA methylation has been postulated to link AME and late-onset diseases. This study aimed to investigate whether and to what extent the hepatic DNA methylome was perturbed prior to the development of NAFLD in offspring exposed to AME in mice. AME constituted maternal Western diet and late-gestational stress. Male offspring livers at birth (d0) and weaning (d21) were used for evaluating the DNA methylome and transcriptome using the reduced representation of bisulfite sequencing and RNA-seq, respectively. We found AME caused 5879 differentially methylated regions (DMRs) and zero differentially expressed genes (DEGs) at d0 and 2970 and 123, respectively, at d21. The majority of the DMRs were distal to gene transcription start sites and did not correlate with DEGs. The DEGs at d21 were significantly enriched in GO biological processes characteristic of liver metabolic functions. In conclusion, AME drove changes in the hepatic DNA methylome, which preceded perturbations in the hepatic metabolic transcriptome, which preceded the onset of NAFLD. We speculate that subtle impacts on dynamic enhancers lead to long-range regulatory changes that manifest over time as gene network alternations and increase the incidence of NAFLD later in life.
format Online
Article
Text
id pubmed-10180730
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-101807302023-05-13 Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring Fu, Qi Cheung, Warren A. Majnik, Amber V. Ke, Xingrao Pastinen, Tomi Lane, Robert H. Nutrients Article Exposure to adverse early-life environments (AME) increases the incidence of developing adult-onset non-alcoholic fatty liver disease (NAFLD). DNA methylation has been postulated to link AME and late-onset diseases. This study aimed to investigate whether and to what extent the hepatic DNA methylome was perturbed prior to the development of NAFLD in offspring exposed to AME in mice. AME constituted maternal Western diet and late-gestational stress. Male offspring livers at birth (d0) and weaning (d21) were used for evaluating the DNA methylome and transcriptome using the reduced representation of bisulfite sequencing and RNA-seq, respectively. We found AME caused 5879 differentially methylated regions (DMRs) and zero differentially expressed genes (DEGs) at d0 and 2970 and 123, respectively, at d21. The majority of the DMRs were distal to gene transcription start sites and did not correlate with DEGs. The DEGs at d21 were significantly enriched in GO biological processes characteristic of liver metabolic functions. In conclusion, AME drove changes in the hepatic DNA methylome, which preceded perturbations in the hepatic metabolic transcriptome, which preceded the onset of NAFLD. We speculate that subtle impacts on dynamic enhancers lead to long-range regulatory changes that manifest over time as gene network alternations and increase the incidence of NAFLD later in life. MDPI 2023-04-30 /pmc/articles/PMC10180730/ /pubmed/37432267 http://dx.doi.org/10.3390/nu15092167 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fu, Qi
Cheung, Warren A.
Majnik, Amber V.
Ke, Xingrao
Pastinen, Tomi
Lane, Robert H.
Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring
title Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring
title_full Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring
title_fullStr Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring
title_full_unstemmed Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring
title_short Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring
title_sort adverse maternal environments perturb hepatic dna methylome and transcriptome prior to the adult-onset non-alcoholic fatty liver disease in mouse offspring
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180730/
https://www.ncbi.nlm.nih.gov/pubmed/37432267
http://dx.doi.org/10.3390/nu15092167
work_keys_str_mv AT fuqi adversematernalenvironmentsperturbhepaticdnamethylomeandtranscriptomepriortotheadultonsetnonalcoholicfattyliverdiseaseinmouseoffspring
AT cheungwarrena adversematernalenvironmentsperturbhepaticdnamethylomeandtranscriptomepriortotheadultonsetnonalcoholicfattyliverdiseaseinmouseoffspring
AT majnikamberv adversematernalenvironmentsperturbhepaticdnamethylomeandtranscriptomepriortotheadultonsetnonalcoholicfattyliverdiseaseinmouseoffspring
AT kexingrao adversematernalenvironmentsperturbhepaticdnamethylomeandtranscriptomepriortotheadultonsetnonalcoholicfattyliverdiseaseinmouseoffspring
AT pastinentomi adversematernalenvironmentsperturbhepaticdnamethylomeandtranscriptomepriortotheadultonsetnonalcoholicfattyliverdiseaseinmouseoffspring
AT laneroberth adversematernalenvironmentsperturbhepaticdnamethylomeandtranscriptomepriortotheadultonsetnonalcoholicfattyliverdiseaseinmouseoffspring