Abstract

We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n = 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n = 12) continued their usual behaviours. FKBP5 methylation was measured in GSAT and ASAT using pyrosequencing. SNP and gene expression analyses were conducted using quantitative real-time PCR. Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7. When stratified based on the rs1360780 SNP, participants with the CT genotype displayed FKBP5 hypermethylation in GSAT (p < 0.05), and ASAT displayed in both CC and CT carriers. CC allele carriers displayed improved cardiorespiratory fitness, insulin sensitivity, gynoid fat mass, and waist circumference (p < 0.05) in response to exercise training, and these parameters were attenuated in women with the CT genotype. These findings provide a basis for future studies in larger cohorts, which should assess whether FKBP5 methylation and/or genetic variants such as the rs1360780 SNP could have a significant impact on responsiveness to exercise interventions.

Details

Title
A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity
Author
Willmer, Tarryn 1 ; Oosthuizen, Amberly 2 ; Dias, Stephanie 2 ; Mendham, Amy E. 3 ; Goedecke, Julia H. 4 ; Pheiffer, Carmen 5 

 South African Medical Research Council, Biomedical Research and Innovation Platform, Tygerberg, South Africa (GRID:grid.415021.3) (ISNI:0000 0000 9155 0024); University of Stellenbosch, Division of Medical Physiology, Centre for Cardiometabolic Research in Africa (CARMA), Faculty of Medicine and Health Sciences, Tygerberg, South Africa (GRID:grid.11956.3a) (ISNI:0000 0001 2214 904X) 
 South African Medical Research Council, Biomedical Research and Innovation Platform, Tygerberg, South Africa (GRID:grid.415021.3) (ISNI:0000 0000 9155 0024) 
 University of the Witwatersrand, South African Medical Research Council/WITS Developmental Pathways for Health Research Unit (DPHRU), Department of Paediatrics, School of Clinical Medicine, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135); University of Cape Town, Division of Physiological Sciences, Health Through Physical Activity, Lifestyle and Sport Research Centre (HPALS), Department of Human Biology, Faculty of Health Sciences, FIMS International Collaborating Centre of Sports Medicine, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151) 
 University of Cape Town, Division of Physiological Sciences, Health Through Physical Activity, Lifestyle and Sport Research Centre (HPALS), Department of Human Biology, Faculty of Health Sciences, FIMS International Collaborating Centre of Sports Medicine, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151); South African Medical Research Council, Non-Communicable Diseases Research Unit, Tygerberg, 7505, Cape Town, South Africa (GRID:grid.415021.3) (ISNI:0000 0000 9155 0024) 
 South African Medical Research Council, Biomedical Research and Innovation Platform, Tygerberg, South Africa (GRID:grid.415021.3) (ISNI:0000 0000 9155 0024); University of Stellenbosch, Division of Medical Physiology, Centre for Cardiometabolic Research in Africa (CARMA), Faculty of Medicine and Health Sciences, Tygerberg, South Africa (GRID:grid.11956.3a) (ISNI:0000 0001 2214 904X); University of Pretoria, Department of Obstetrics and Gynaecology, Faculty of Health Sciences, Pretoria, South Africa (GRID:grid.49697.35) (ISNI:0000 0001 2107 2298) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2687919060
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.