Fasting unmasks differential fat and muscle transcriptional regulation of metabolic gene sets in low versus normal birth weight men.
Adipose Tissue
/ metabolism
Adult
Binding Sites
Biomarkers
Birth Weight
DNA Methylation
Energy Metabolism
/ genetics
Fasting
Gene Expression Profiling
Gene Expression Regulation
Genome-Wide Association Study
Humans
Male
Models, Biological
Muscle, Skeletal
/ metabolism
Nucleotide Motifs
Protein Binding
Sex Factors
Transcription Factors
Transcription, Genetic
Young Adult
Birth weight
Epigenetics
Fasting
Metabolism
Transcriptomics
Type 2 diabetes
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
12
06
2019
revised:
19
07
2019
accepted:
06
08
2019
pubmed:
24
8
2019
medline:
6
2
2020
entrez:
24
8
2019
Statut:
ppublish
Résumé
Individuals born with low birth weight (LBW) have an increased risk of metabolic diseases when exposed to diets rich in calories and fat but may respond to fasting in a metabolically preferential manner. We hypothesized that impaired foetal growth is associated with differential regulation of gene expression and epigenetics in metabolic tissues in response to fasting in young adulthood. Genome-wide expression and DNA methylation were analysed in subcutaneous adipose tissue (SAT) and skeletal muscle from LBW and normal birth weight (NBW) men after 36 h fasting and after an isocaloric control study using microarrays. Transcriptome analyses revealed that expression of genes involved in oxidative phosphorylation (OXPHOS) and other key metabolic pathways were lower in SAT from LBW vs NBW men after the control study, but paradoxically higher in LBW vs NBW men after 36 h fasting. Thus, fasting was associated with downregulated OXPHOS and metabolic gene sets in NBW men only. Likewise, in skeletal muscle only NBW men downregulated OXPHOS genes with fasting. Few epigenetic changes were observed in SAT and muscle between the groups. Our results provide insights into the molecular mechanisms in muscle and adipose tissue governing a differential metabolic response in subjects with impaired foetal growth when exposed to fasting in adulthood. The results support the concept of developmental programming of metabolic diseases including type 2 diabetes. FUND: The Swedish Research Council, the Danish Council for Strategic Research, the Novo Nordisk foundation, the Swedish Foundation for Strategic Research, The European Foundation for the Study of Diabetes, The EU 6th Framework EXGENESIS grant and Rigshospitalet.
Sections du résumé
BACKGROUND
BACKGROUND
Individuals born with low birth weight (LBW) have an increased risk of metabolic diseases when exposed to diets rich in calories and fat but may respond to fasting in a metabolically preferential manner. We hypothesized that impaired foetal growth is associated with differential regulation of gene expression and epigenetics in metabolic tissues in response to fasting in young adulthood.
METHODS
METHODS
Genome-wide expression and DNA methylation were analysed in subcutaneous adipose tissue (SAT) and skeletal muscle from LBW and normal birth weight (NBW) men after 36 h fasting and after an isocaloric control study using microarrays.
FINDINGS
RESULTS
Transcriptome analyses revealed that expression of genes involved in oxidative phosphorylation (OXPHOS) and other key metabolic pathways were lower in SAT from LBW vs NBW men after the control study, but paradoxically higher in LBW vs NBW men after 36 h fasting. Thus, fasting was associated with downregulated OXPHOS and metabolic gene sets in NBW men only. Likewise, in skeletal muscle only NBW men downregulated OXPHOS genes with fasting. Few epigenetic changes were observed in SAT and muscle between the groups.
INTERPRETATION
CONCLUSIONS
Our results provide insights into the molecular mechanisms in muscle and adipose tissue governing a differential metabolic response in subjects with impaired foetal growth when exposed to fasting in adulthood. The results support the concept of developmental programming of metabolic diseases including type 2 diabetes. FUND: The Swedish Research Council, the Danish Council for Strategic Research, the Novo Nordisk foundation, the Swedish Foundation for Strategic Research, The European Foundation for the Study of Diabetes, The EU 6th Framework EXGENESIS grant and Rigshospitalet.
Identifiants
pubmed: 31439477
pii: S2352-3964(19)30533-X
doi: 10.1016/j.ebiom.2019.08.017
pmc: PMC6796584
pii:
doi:
Substances chimiques
Biomarkers
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
341-351Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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