Epigenetic patterns in successful weight loss maintainers: a pilot study

Abstract

DNA methylation changes occur in animal models of calorie restriction, simulating human dieting, and in human subjects undergoing behavioral weight loss interventions. This suggests that obese (OB) individuals may possess unique epigenetic patterns that may vary with weight loss. Here, we examine whether methylation patterns in leukocytes differ in individuals who lost sufficient weight to go from OB to normal weight (NW; successful weight loss maintainers; SWLMs) vs currently OB or NW individuals. This study examined peripheral blood mononuclear cell (PBMC) methylation patterns in NW (n=16, current/lifetime BMI 18.5-24.9) and OB individuals (n=16, current body mass index (BMI)⩾30), and SWLM (n=16, current BMI 18.5-24.9, lifetime maximum BMI ⩾30, average weight loss 57.4 lbs) using an Illumina Infinium HumanMethylation450 BeadArray. No leukocyte population-adjusted epigenome-wide analyses were significant; however, potentially differentially methylated loci across the groups were observed in ryanodine receptor-1 (RYR1; P=1.54E-6), myelin protein zero-like 3 (MPZL3; P=4.70E-6) and alpha 3c tubulin (TUBA3C; P=4.78E-6). In 32 obesity-related candidate genes, differential methylation patterns were found in brain-derived neurotrophic factor (BDNF; gene-wide P=0.00018). In RYR1, TUBA3C and BDNF, SWLM differed from OB but not NW. In this preliminary investigation, leukocyte SWLM DNA methylation patterns more closely resembled NW than OB individuals in three gene regions. These results suggest that PBMC methylation is associated with weight status.

Figure 1

Manhattan plot for differences in methylation status across groups of NW, OB, and SWLM participants at 384 477 autosomal, non-single-nucleotide polymorphism (SNP)-associated CpG loci. Red dots indicate the top three CpG loci by p-value, which were located in the RYR1 region on chromosome 19, in the MPZL3 region on chromosome 11, and in the TUBA3C region on chromosome 13.

Figure 2

Differences in PBMC methylation status by group (NW, OB, and SWLM) at A) RYR1 cg12227210 (p=0.0075; for OB vs SWLM, p=9.61×10⁻⁴; NW vs SWLM, p=0.44; NW vs OB, p=0.026); B) RYR1 cg26963641 (p=0.012; for OB vs SWLM, p=0.079; NW vs SWLM, p=0.86; NW vs OB, p=0.016); C) RYR1 cg05254946 (p=1.54 ×10⁻⁶; for OB vs SWLM, p=8.76×10⁻⁶; NW vs SWLM, p=0.11; NW vs OB, p=3.30 ×10⁻⁵); D) MPZL3 cg19069882 (p=4.70 ×10⁻⁶; for OB vs SWLM, p=5.58 ×10⁻³; NW vs SWLM, p=2.75 ×10⁻⁵; NW vs OB, p=0.03); E) TUBA3C cg22274414 (p=4.78 ×10⁻⁶; for OB vs SWLM, p=1.79 ×10⁻⁵; NW vs SWLM, p=0.30; NW vs OB, p=1.32 ×10⁻⁴); and F) BDNF cg06025631 (p=6.11×10⁻⁴; for OB vs SWLM, p=0.0029; NW vs SWLM, p=0.47; NW vs OB, p=0.0015).