Table 2.
Candidate-gene methylation studies under lifestyle intervention.
| Lifestyle intervention | Participants | Methods | Gene(s) | Results | Reference |
|---|---|---|---|---|---|
| weight loss diet interventions varying in macronutrient components/2-years
Aim: investigate the association of DNA methylation at the CPT1A gene with reductions in triglycerides and triglyceride-rich lipoproteins (TRLs) in response to weight loss diet interventions |
528 participants (BMI = 32,5 kg/m2, Age = 52 years, 305 female/223 male) | IlluminaNovaSeq6000 platform by a high-resolution methyl-capture sequencing (MCC-Seq) | CPT1A | Dietary fat intake significantly modified the association between baseline DNA methylation at CPT1A and 2-year changes in total plasma triglycerides, independent of concurrent weight loss; with low-fat diet, a higher regional DNAm level at CPT1A was associated with a greater reduction in total plasma triglycerides at 2 years compared to a high-fat diet | Li et al. 2023 (37) |
| energy-reduced diets/2-year
Aim: examine the impact of the NFATC2IP rs11150675 genotype on adiposity changes |
692 overweight and obese people (BMI = 25-40 kg/m2, mean Age = 51.4 years, 61.1% females) |
OpenArray SNP Genotyping System & Illumina HumanMethylation 450K Bead Chips Tissue: blood |
NFATC2IP | dietary fat intake significantly modified the effect of the genetic, epigenetic and transcriptional variations at the NFATC2IP locus of weight change; NFATC2IP methylation mediated 52.8% of its genotypic effect in response to a high-fat diet rather than a low-fat diet |
Sun et al. 2018 (38) |
| weight loss diet intervention/2-years
Aim: investigate whether baseline blood DNA methylation levels in TXNIP can be associated with glycemic characteristics and their changes in response to weight loss interventions |
639 adult participants with overweight or obesity (BMI= 25-40 kg/m2,mean age= 50.1-52,2) | IlluminaNovaSeq6000 platform by a high-resolution methyl-capture sequencing (MCC-Seq) immunoassay with chemiluminescent detection on an Illumina analyzer Tissue: blood |
TXNIP | higher regional DNA methylation at TXNIP was significantly correlated with lower fasting glucose, HbA1c, and HOMA-IR at baseline; dietary protein intakes significantly modified the relation between regional DNA-methylation level at TXNIP and changes in insulin and HOMA-IR at 6 months |
Li et al. 2022 (39) |
| supervised aerobic & resistance training/12-weeks
Aim: investigate ASAT and GSAT DNA methylation of FKBP5 in response to an exercise intervention |
19 African women with obesity (BMI = 34.9 kg/m2, mean age = 22) 12 controls continued their usual behaviour (BMI = 33.0 kg/m2, mean age = 24) | Pyrosequencing, SNP & gene expression analyses with real-time PCR Tissue: GSAT & ASAT |
FKBP5 | Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7; CC allele carriers displayed improved cardiorespiratory fitness, insulin sensitivity, gynoid fat mass, and waist circumference |
Willmer et al. 2022 (36) |
| lifestyle intervention (Care Call programme)/6 months
Aim: investigated whether a lifestyle intervention could influence expression and DNA methylation of diabetes-related genes |
20 participants with impaired glucose regulation (10 females/10 males, Age = 18–80) | Pyrosequencing Tissue: blood & adipose tissue |
CAV1 | intervention resulted in opposite direction changes in fat tissue and blood for CAV1 expression and DNA methylation and these changes were correlated between tissues | Fachim et al. 2020 (40) |
| BWRP/3-week
Aim: evaluate the DNA methylation status of seven clock genes |
45 obese adolescents (BMI = 37.5 kg/m2, 28 female/17male, Age = 15.8 ± 1.4) | Pyrosequencing Tissue: blood |
CLOCK, PER1-3 & CRY1-2 | BWRP changes in the methylation levels of CLOCK, CRY2 and PER2 genes; hypermethylation of CLOCK and PER3 genes in males and in subjects with metabolic syndrome |
Rigamonti et al. 2022 (41) |
| weight loss program intervention/6-month
Aim: quantify FTO whole blood DNA methylation & investigate the relationship between body composition, exercise capacity & blood parameters |
18 female participants (BMI: 33.5 ± 6.2 kg/m2, mean age, 50.6 ±12.1 years) | Pyrosequencing Tissue: blood |
FTO | Methylation rate was significantly decreased in the normal treatment group in CpG1; treatment group containing resistance training CpG3 was increased |
Nishida et al. 2020 (42) |
| Mediterranean low-carbohydrate/fat diet with/without PA/18-month
Aim: examine the effect of lifestyle interventions on DNA-methylation of nonalcoholic fatty-liver disease related genes |
120 participants from the CENTRAL RCT, (92% men; BMI = 30.2 kg/m2, age = 49 ± 9 years) | Illumina HumanMethylation 850K Bead Chips; Single-nucleotide polymorphisms genotyped by TaqMan assays Tissue: blood |
AC074286.1, CRACR2A, A2MP1, FARP1 | Baseline-IHF% was inversely correlated with DNA-methylation within AC074286.1, CRACR2A, A2MP1, FARP1; differential DNA-methylation patterns were observed between diets at A2MP1 and between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs |
Yaskolka Meir et al. 2021 (23) |
| VLCKD, HCD or BS/4–6 months
Aim: evaluate the methylation levels of ACE2 gene, the main entry receptor of SARS-CoV-2, in different depots of AT (subcutaneous and visceral) and PBMCs |
45 obese patients (23 female/22 male) compared with non-obese patients (9 female/9 men) | Illumina HumanMethylation 450K Bead Chips Tissue: SAT, VAT, PBMCs |
ACE2 | VAT from patients with obesity showed higher ACE2 methylation levels, mirrored in PBMCs but not in SAT; observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS; observed DNA methylation pattern was inversely correlated with ACE2 expression |
Izquierdo et al. 2022 (34) |
This table summarize our candidate-gene methylation studies under lifestyle intervention. SNP, Single nucleotide polymorphism; NFATC2IP, Nuclear factor of activated T cells 2 interacting protein; ASAT, abdominal subcutaneous; GSAT, gluteal subcutaneous adipose tissue; PCR, polymerase chain reaction; FKBP5, FKBP Prolyl Isomerase 5; CAV1, Caveolin 1; BWRP, multidisciplinary body weight reduction program; CLOCK, Circadian locomoter output cycles protein kaput; CRY2, Cryptochrome circadian regulator 2; PER2/3, Period circadian regulator 2/3; FTO, Fat mass and obesity-related; IHF, intrahepatic fat; PA, physical activity; CRACR2A, Calcium release activated channel regulator 2A; A2MP1, Alpha-2-macroglobulin pseudogene 1; FARP1, FERM, ARH/RhoGEF and pleckstrin domain protein 1; HCD, a balanced hypocaloric diet; VAT, visceral adipose tissue; SAT, subcutaneous adipose tissue; BS, bariatric surgery; ACE2, Angiotensin converting enzyme 2.