DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance
Date
2020-09-21
Journal Title
Journal ISSN
Volume Title
Publisher
BMC (part of Springer Nature)
Abstract
Background: Disruption of the hypothalamic–pituitary–adrenal (HPA) axis, a neuroendocrine system associated
with the stress response, has been hypothesized to contribute to obesity development. This may be mediated
through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this
study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor
(GR) and its co-chaperone, FK506-binding protein 51 kDa (FKBP5), both key modulators of the HPA axis.
Methods: Abdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies
were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA
methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively.
Spearman’s correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear
regression were performed to evaluate the associations between DNA methylation, messenger RNA (mRNA)
expression and key indices of obesity and metabolic dysfunction.
Results: Two CpG dinucleotides within intron 7 of FKBP5 were hypermethylated in both ASAT and GSAT in obese
compared to normal weight women, while no differences in GR methylation were observed. Higher percentage
methylation of the two FKBP5 CpG sites correlated with adiposity (body mass index and waist circumference),
insulin resistance (homeostasis model for insulin resistance, fasting insulin and plasma adipokines) and systemic
inflammation (c-reactive protein) in both adipose depots. GR and FKBP5 mRNA levels were lower in GSAT, but not
ASAT, of obese compared to normal weight women. Moreover, FKBP5 mRNA levels were inversely correlated with
DNA methylation and positively associated with adiposity, metabolic and inflammatory parameters.
Conclusions: These findings associate dysregulated FKBP5 methylation and mRNA expression with obesity and
insulin resistance in South African women. Additional studies are required to assess the longitudinal association of
FKBP5 with obesity and associated co-morbidities in large population-based samples.
Description
CITATION: Willmer, T., et al. 2020. DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance. Clinical Epigenetics, 12:141, doi:10.1186/s13148-020-00932-3.
The original publication is available at https://clinicalepigeneticsjournal.biomedcentral.com
The original publication is available at https://clinicalepigeneticsjournal.biomedcentral.com
Keywords
Obesity, DNA -- Methylation, Insulin resistance, Glucocorticoid receptor, Adipose tissue
Citation
Willmer, T., et al. 2020. DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance. Clinical Epigenetics, 12:141, doi:10.1186/s13148-020-00932-3