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Associations of plasma betaine, plasma choline, choline intake, and MTHFR polymorphism (rs1801133) with anthropometric parameters of healthy adults are sex‐dependent
AbstractBackgroundCholine and its metabolites apppear to have relationships with body mass index (BMI), body fat, and body weight, but the research results have proved inconsistent. We thus investigated the associations of plasma levels of trimethylamine N‐oxide (TMAO), choline, and betaine with anthropometric measurements, including modulatory effects of genetics and diet.MethodsThe study was performed on a group of 421 adults, aged 20–40 years, who had been recruited in Poland. Plasma concentrations of choline, betaine, and TMAO were determined using reverse‐phase ultra‐high‐performance liquid chromatography electrospray ionisation mass spectrometry. The following polymorphisms were genotyped using TaqMan probes: rs180113 (MTHFR), rs70991108 (DHFR), rs2236225 (MTHFD1), and rs7946 and rs12325817 (PEMT). We employed multivariate linear regression to examine the associations between anthropometric measurements, one‐carbon metabolism metabolites, and genotypes.ResultsHigher plasma choline was associated with higher BMI (β = 0.17; p < 0.01), body weight (β = 0.11; p < 0.05), body fat mass (FM) (β = 0.10; p < 0.05), and waist circumference (WC) (β = 0.14; p < 0.01), whereas higher choline intake was associated with lower body FM (β = −0.14; p < 0.01) and lower WC (β = −0.12; p < 0.01). After stratification by sex, plasma betaine was found to be associated with lower BMI (β = −0.20; p < 0.05) and body weight (β = −0.16; p < 0.05) in men only, whereas choline intake was associated with lower body FM (β = −0.19; p < 0.05) and waist‐to‐hip ratio (WHR) (β = −0.19; p < 0.05) and MTHFR CC genotype was associated with WHR (β = 0.15; p < 0.05) in women only.ConclusionsHigher plasma betaine and higher dietary choline are associated with lower FM and body weight, whereas higher plasma choline is positively associated with body weight status and adiposity. Moreover, these associations appear to be sex‐specific.
Betaine and B12 Intake, Glutathione Concentration, and MTHFR, PEMT, and MTHFD1 Genotypes Are Associated with Diabetes-Related Parameters in Polish Adults
Mitochondrial DNA and Epigenetics: Investigating Interactions with the One‐Carbon Metabolism in Obesity
Mitochondrial DNA copy number (mtDNAcn) has been proposed for use as a surrogate biomarker of mitochondrial health, and evidence suggests that mtDNA might be methylated. Intermediates of the one‐carbon cycle (1CC), which is duplicated in the cytoplasm and mitochondria, have a major role in modulating the impact of diet on the epigenome. Moreover, epigenetic pathways and the redox system are linked by the metabolism of glutathione (GSH). In a cohort of 101 normal‐weight and 97 overweight/obese subjects, we evaluated mtDNAcn and methylation levels in both mitochondrial and nuclear areas to test the association of these marks with body weight, metabolic profile, and availability of 1CC intermediates associated with diet. Body composition was associated with 1CC intermediate availability. Reduced levels of GSH were measured in the overweight/obese group (p = 1.3∗10−5). A high BMI was associated with lower LINE‐1 (p = 0.004) and nominally lower methylenetetrahydrofolate reductase (MTHFR) gene methylation (p = 0.047). mtDNAcn was lower in overweight/obese subjects (p = 0.004) and independently correlated with MTHFR methylation levels (p = 0.005) but not to LINE‐1 methylation levels (p = 0.086). DNA methylation has been detected in the light strand but not in the heavy strand of the mtDNA. Although mtDNA methylation in the light strand did not differ between overweight/obese and normal‐weight subjects, it was nominally correlated with homocysteine levels (p = 0.035) and MTHFR methylation (p = 0.033). This evidence suggests that increased body weight might perturb mitochondrial‐nuclear homeostasis affecting the availability of nutrients acting as intermediates of the one‐carbon cycle.