Obesity-induced insulin resistance via changes in the DNA methylation profile of insulin pathway genes.
DNA methylation
insulin resistance
insulin signaling pathway
obesity
Journal
Advances in clinical and experimental medicine : official organ Wroclaw Medical University
ISSN: 1899-5276
Titre abrégé: Adv Clin Exp Med
Pays: Poland
ID NLM: 101138582
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
pubmed:
26
11
2019
medline:
10
3
2020
entrez:
26
11
2019
Statut:
ppublish
Résumé
Obesity has been shown to play a key role in the development of insulin resistance (IR). Abundant data implicate obesity in DNA hypermethylation at global and site-specific levels, including genes regulating insulin sensitivity. Deregulation of epigenetic marks implicates gene expression and changes in cell metabolism. Our previous reports demonstrated that the strongest risk factor in the development of IR is BMI; accordingly, the objective of this study was to investigate the effect of obesity on DNA methylation and insulin sensitivity. A study was carried out on lymphocytes (N-34) and visceral adipose tissue (VAT; N-35) of insulin-resistant subjects and healthy controls. Genetic material (DNA and RNA) was extracted from cells. Global and site-specific DNA methylation was analyzed with the use of restriction enzymes followed by real-time polymerase chain reaction (PCR). Gene expression was analyzed as relative mRNA level normalized to a housekeeping gene. Global DNA methylation increased in both types of tissue in obese and insulin-resistant individuals and correlated positively with IR. Two of the 3 investigated promoters of insulin pathway genes were hypermethylated, which correlated negatively with gene expression and positively with IR. The DNMT3a gene was upregulated in obese insulin-resistant individuals in both types of tissues and correlated positively with global DNA methylation. DNA methylation profile changed depending on body mass index (BMI) and influenced glucose metabolism and insulin sensitivity in VAT.
Sections du résumé
BACKGROUND
BACKGROUND
Obesity has been shown to play a key role in the development of insulin resistance (IR). Abundant data implicate obesity in DNA hypermethylation at global and site-specific levels, including genes regulating insulin sensitivity. Deregulation of epigenetic marks implicates gene expression and changes in cell metabolism.
OBJECTIVES
OBJECTIVE
Our previous reports demonstrated that the strongest risk factor in the development of IR is BMI; accordingly, the objective of this study was to investigate the effect of obesity on DNA methylation and insulin sensitivity.
MATERIAL AND METHODS
METHODS
A study was carried out on lymphocytes (N-34) and visceral adipose tissue (VAT; N-35) of insulin-resistant subjects and healthy controls. Genetic material (DNA and RNA) was extracted from cells. Global and site-specific DNA methylation was analyzed with the use of restriction enzymes followed by real-time polymerase chain reaction (PCR). Gene expression was analyzed as relative mRNA level normalized to a housekeeping gene.
RESULTS
RESULTS
Global DNA methylation increased in both types of tissue in obese and insulin-resistant individuals and correlated positively with IR. Two of the 3 investigated promoters of insulin pathway genes were hypermethylated, which correlated negatively with gene expression and positively with IR. The DNMT3a gene was upregulated in obese insulin-resistant individuals in both types of tissues and correlated positively with global DNA methylation.
CONCLUSIONS
CONCLUSIONS
DNA methylation profile changed depending on body mass index (BMI) and influenced glucose metabolism and insulin sensitivity in VAT.
Identifiants
pubmed: 31766080
doi: 10.17219/acem/110321
doi:
Substances chimiques
Insulin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM