Changes in Body Composition and FTO Whole Blood DNA Methylation Among Japanese Women: A Randomized Clinical Trial of Weight-Loss Program

Abstract

Objective

DNA methylation is an epigenetic mechanism that regulates gene expression. The obesity-related (FTO) gene is the first gene found to be associated with fat mass and obesity. However, no studies have examined the relationship between weight-loss intervention effect and FTO methylation in obese individuals with whole blood DNA. The purpose of this study was to quantify FTO whole blood DNA methylation and investigate the relationship between body composition, exercise capacity, and blood parameters with a 6-month weight-loss program intervention.

Participants and Methods

Eighteen female participants (mean age, 50.6 ±12.1 years, body mass index (BMI), 33.5 ± 6.2 kg/m²) who completed a 6-month weight-loss program at the obesity outpatient department at the Health Science Center of Kansai Medical University Hospital from March 2017 to October 2018 were included in the analysis. Participants were randomized into a normal treatment group (NTG) and a group with additional resistance training (RTG). Body composition, exercise tolerance and metabolic index were measured in each participant. DNA methylation status in whole blood samples was determined using pyrosequencing. All measurements were taken during the first visit and at the 6-month post-intervention visit.

Results

The methylation rate was significantly decreased in the NTG in CpG1 (p=0.011) and total value of CpG (p=0.011), whereas in the treatment group containing resistance training (RTG), CpG3 (p=0.038) was increased significantly. Furthermore, the independent factors that determine %CpG3 of RTG were visceral fat area change rate (%VFA) (β = −0.568, P = 0.007, R2 = 0.527) and resistance training (β = 0.517, P = 0.012, R2 = 0.527), which have been extracted.

Conclusion

A 6-month weight-loss program, including resistance training, may be associated with decreased visceral fat area changes and increased RTG CpG3 methylation changes. However, further replication studies with larger sample sizes are warranted to verify the findings of this study.

Keywords:

• epigenetics
• obesity
• body composition
• resistance training

Abbreviations

FTO, fat mass and obesity-associated gene; RT, resistance training; NTG, normal treatment group; RTG, RT-added group; BMI, body mass index; VFA, visceral fat area; SFA, subcutaneous fat area; AT, anaerobic threshold; VO₂, peak maximum oxygen uptake; HOMA-IR, homeostasis model assessment of insulin resistance; CpG, cytosine guanine dinucleotide; UTR, untranslated region; TG, triglyceride; T2D, type 2 diabetes; Mets, metabolic syndrome.

Acknowledgments

The authors thank all patients who took role in this study.

Ethics approval and informed consent

This study was conducted with approval from the Kansai Medical University Ethics Committee. All participants provided written, informed consent for participation in the study. This study was conducted in accordance with the Declaration of Helsinki.

Disclosure

The authors report no conflicts of interest related to this work.

Additional information

Funding

This project was supported by the staff of the Health Science Center at Kansai Medical University Hospital.