Journal
INTERNATIONAL JOURNAL OF OBESITY
Volume 43, Issue 5, Pages 974-988Publisher
SPRINGERNATURE
DOI: 10.1038/s41366-018-0254-3
Keywords
-
Categories
Funding
- Medical Research Council [MC_UU_12011/4, MC_UP_A620_1017, MC_ ST_U12055]
- British Heart Foundation [RG/15/17/3174, RG/07/009]
- Nestec [BIDG/2013/00456]
- NIHR Musculoskeletal Biomedical Research Unit
- University of Oxford
- NIHR Southampton Biomedical Research Centre
- University of Southampton
- University Hospital Southampton NHS Foundation Trust
- National Institute for Health Research [NF-SI-0515-10042]
- National Institute for Health Research (NIHR Southampton Biomedical Research Centre)
- European Union [289346, 613977]
- US National Institute On Aging of the National Institutes of Health [U24AG047867]
- UK Economic and Social Research Council [ES/M00919X/1]
- Biotechnology and Biological Sciences Research Council [ES/M00919X/1]
- European Commission [244995]
- Australian National Health and Medical Research Council (NHMRC) [1059711]
- National Health and Medical Research Council [353514, 403981]
- University of Western Australia (UWA)
- Raine Medical Research Foundation
- Telethon Kids Institute
- UWA Faculty of Medicine, Dentistry and Health Sciences
- Curtin University
- Edith Cowan University
- MRC [MC_U147585819, G0400491, MC_U147585827, MC_UP_A620_1017, MC_UU_12011/2, MC_UU_12011/4, MC_UP_A620_1015] Funding Source: UKRI
Ask authors/readers for more resources
Background The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. Methods DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women's Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. Results Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 67 years (p = 0.0001) and % fat mass at 6-7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6-7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p <= 0.001), waist circumference (p = 0.011), subcutaneous fat (p <= 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. Conclusions These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available