Mitochondrial DNA in Visceral Adipose Tissue in Severe Obesity: From Copy Number to D-Loop Methylation.
DNA methylation
TFAM
diabetes
epigenetics
metabolic syndrome
nutrigenomics
Journal
Frontiers in bioscience (Landmark edition)
ISSN: 2768-6698
Titre abrégé: Front Biosci (Landmark Ed)
Pays: Singapore
ID NLM: 101612996
Informations de publication
Date de publication:
31 05 2022
31 05 2022
Historique:
received:
28
03
2022
revised:
13
05
2022
accepted:
16
05
2022
entrez:
24
6
2022
pubmed:
25
6
2022
medline:
28
6
2022
Statut:
ppublish
Résumé
Peripheral alterations of mitochondrial DNA copy number (mtDNAcn) in obesity and associated co-morbidities have been previously shown. Furthermore, the possibility that methylation could occur in the mtDNA (in particular in the displacement loop, D-Loop) and regulate its functions has been raised. However, limited data about mtDNA methylation in adipose tissue are currently available. Since a strict crosstalk between the nucleus and mitochondria exists, especially in terms of the one-carbon cycle (that supports methylation reactions in the cell), we investigated methylation in selected areas of the mitochondrial and nuclear DNA and their expression in visceral adipose tissue (VAT) samples of patients with severe obesity. VAT biopsies were collected from surgery patients to isolate DNA and RNA. Gene expression and mtDNAcn were assessed through qPCR. DNA methylation in both nuclear and mitochondrial areas were determined through bisulfite pyrosequencing. Methylation levels of the mtDNA were only marginally associated with the obesity degree (higher D-Loop methylation in severe obesity) and were not correlated with mtDNAcn. A significant correlation between D-Loop methylation and LINE-1 methylation was observed in VAT samples, and this was independent from the obesity degree. A progressive reduction of mtDNAcn and increase in This evidence supports the hypothesis that mtDNA alterations occur in obesity and a complex dynamic correlation between mitochondrial and nuclear DNA methylation exists, highlighting the need for further investigations.
Sections du résumé
BACKGROUND
Peripheral alterations of mitochondrial DNA copy number (mtDNAcn) in obesity and associated co-morbidities have been previously shown. Furthermore, the possibility that methylation could occur in the mtDNA (in particular in the displacement loop, D-Loop) and regulate its functions has been raised. However, limited data about mtDNA methylation in adipose tissue are currently available. Since a strict crosstalk between the nucleus and mitochondria exists, especially in terms of the one-carbon cycle (that supports methylation reactions in the cell), we investigated methylation in selected areas of the mitochondrial and nuclear DNA and their expression in visceral adipose tissue (VAT) samples of patients with severe obesity.
METHODS
VAT biopsies were collected from surgery patients to isolate DNA and RNA. Gene expression and mtDNAcn were assessed through qPCR. DNA methylation in both nuclear and mitochondrial areas were determined through bisulfite pyrosequencing.
RESULTS
Methylation levels of the mtDNA were only marginally associated with the obesity degree (higher D-Loop methylation in severe obesity) and were not correlated with mtDNAcn. A significant correlation between D-Loop methylation and LINE-1 methylation was observed in VAT samples, and this was independent from the obesity degree. A progressive reduction of mtDNAcn and increase in
CONCLUSIONS
This evidence supports the hypothesis that mtDNA alterations occur in obesity and a complex dynamic correlation between mitochondrial and nuclear DNA methylation exists, highlighting the need for further investigations.
Identifiants
pubmed: 35748248
pii: S2768-6701(22)00531-7
doi: 10.31083/j.fbl2706172
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
172Informations de copyright
© 2022 The Author(s). Published by IMR Press.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest. LB, AG and RG are serving as Guest Editors of this journal. We declare that LB, AG and RG had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to GP.