Abstract
OBJECTIVES:We aimed to test the hypotheses that (i) plasma choline metabolites differ between normal (body mass index (BMI)<25 kg m−2) and overweight (BMI ⩾25 kg m−2) men, and (ii) an elevated BMI alters associations between plasma choline metabolites and indicators of metabolic stress.DESIGN:This was a cross-sectional study. A one-time fasting blood sample was obtained for measurements of the choline metabolites and metabolic stress indicators (that is, serum alanine aminotransferase (ALT), glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and homocysteine), and for genotype determination.SUBJECTS:The analysis was conducted with 237 Mexican American men with a median age of 22 years.RESULTS:Compared with men with a normal BMI (n=98), those with an elevated BMI (n=139) had 6% lower (P=0.049) plasma betaine and an 11% lower (P=0.002) plasma betaine to choline ratio. Among men with an elevated BMI, plasma betaine and the plasma betaine to choline ratio positively associated (P⩽0.044) with a favorable serum cholesterol profile, and inversely associated (P=0.001) with serum ALT, a marker of liver dysfunction. The phosphatidylethanolamine N-methyltransferase (PEMT) 5465G→A (rs7946) genotype interacted (P⩽0.007) with the plasma betaine to choline ratio to modulate indicators of metabolic stress with stronger inverse associations observed among overweight men with the PEMT 5465GG genotype.CONCLUSIONS:Plasma choline metabolites predict metabolic stress among overweight men often in a genotype-specific manner. The diminished betaine among overweight men coupled with the inverse association between betaine and metabolic stress suggest that betaine supplementation may be effective in mitigating some of the metabolic insults arising from lipid overload.
Highlights
Obesity can lead to a number of metabolic disturbances and increase the risk of metabolic syndrome, type 2 diabetes and cardiovascular diseases.[1,2,3,4,5,6] The metabolic stress imposed by obesity is often indicated by alterations in circulating lipoproteins, triglycerides, glucose and markers of liver function
As genetic variants in one-carbon metabolic genes affect choline metabolism,[21,22,23] we examined the potential modifying effects of these two genetic variants on associations between the plasma choline metabolites and indicators of metabolic stress
An inverse association (P 1⁄4 0.032) was detected men and (iii) the relationship between plasma choline metabolites only among men with phosphatidylethanolamine N-methyltransferase (PEMT) 5465AA genotype. and metabolic stress is frequently genotype-specific. In this cohort of young men, we demonstrate that (i) plasma choline metabolites differ between normal and overweight men, (ii) plasma choline metabolites, especially the ratio of plasma betaine to choline, predict metabolic stress among overweight
Summary
Obesity can lead to a number of metabolic disturbances and increase the risk of metabolic syndrome, type 2 diabetes and cardiovascular diseases.[1,2,3,4,5,6] The metabolic stress imposed by obesity is often indicated by alterations in circulating lipoproteins, triglycerides, glucose and markers of liver function. Obesity manifests as excess lipid deposition in adipose tissue and frequently the liver.[7,8] Studies in rodent models of obesity suggest that hepatic lipid overload results in perturbations in choline-related one-carbon metabolism.[9,10]. An essential nutrient, is a major lipotrophe (that is, nutrient that is involved in the mobilization of fat from liver).[11] Its derivative phosphatidylcholine (Figure 1), which is synthesized from choline via the cytidine diphosphate–choline pathway, is required for the production of hepatic very-low-density lipoprotein and the subsequent export of fat from liver. Choline deficiency results in fatty liver and liver dysfunction, which leads to elevations in serum concentrations of the liver enzyme, alanine aminotransferase (ALT).[12,13] Phosphatidylcholine can be produced via the phosphatidylethanolamine N-methyltransferase (PEMT) pathway where methyl groups associated with S-adenosylmethionine are used to sequentially methylate phosphatidylethanolamine.
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