Abstract

Plasma choline shows associations with plasma glucose and lipids. We studied changes of choline metabolites after oral glucose tolerance test (OGTT) and fat tolerance test (OFTT). Eighteen healthy subjects (mean age 54.3 years; BMI 26.8 kg/m2) underwent 2 tests. First, OFTT (80 g fat) was applied and blood was collected at baseline and 4 h after OFTT. Seven days later, 75 g glucose was applied and blood was collected at baseline and 2 h after OGTT. Plasma concentrations of choline, betaine, trimethylamine N-oxide (TMAO), dimethylglycine, S-adenosylmethionine (SAM), lipids and glucose were measured. After OFTT, plasma choline declined (10.6 to 9.2 µmol/L; p = 0.004), betaine declined (33.4 to 31.7 µmol/L; p = 0.003), TMAO slightly increased (4.1 to 5.6 µmol/L; p = 0.105), glucose declined (5.39 to 4.98 mmol/L; p < 0.001), and triglycerides increased (1.27 to 2.53 mmol/L; p < 0.001). After OGTT, plasma choline increased (10.1 to 11.1 µmol/L; p < 0.001), TMAO declined (4.0 to 3.5 µmol/L; p = 0.029), dimethylglycine declined (2.0 to 1.7 µmol/L; p = 0.005), SAM declined (103 to 96 nmol/L; p = 0.041), but betaine, glucose, and SAM were unchanged. In conclusion, OFTT lowered plasma betaine and choline and caused heterogeneous changes in plasma TMAO. OGTT reduced the flow of methyl groups and plasma TMAO.

Highlights

  • Choline is a precursor of phosphatidylcholine and a methyl donor

  • The methylation reaction mediated by betaine-homocysteine methyltransferase (BHMT) gives dimethylglycine and methionine that is in turn the precursor of the universal methyl donor, S-adenosylmethionine (SAM)

  • Changes of plasma choline and trimethylamine N-oxide (TMAO) from baseline were in opposite directions; plasma choline declined and TMAO increased after oral fat tolerance test (OFTT), while choline increased and TMAO declined after oral glucose tolerance test (OGTT)

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Summary

Introduction

Choline is a precursor of phosphatidylcholine and a methyl donor (via irreversible mitochondrial oxidation to betaine). Betaine is provided by the diet or from choline oxidation. Betaine is an important osmolyte and a methyl donor for homocysteine. The methylation reaction mediated by betaine-homocysteine methyltransferase (BHMT) gives dimethylglycine and methionine that is in turn the precursor of the universal methyl donor, S-adenosylmethionine (SAM). Choline is required for synthesis of phosphatidylcholine that constitutes an integral part of lipoprotein particles and is involved in clearance of fats from blood stream and tissues. High choline intake can abolish the effect of high fat diet on liver steatosis. Plasma concentrations of free choline, betaine, and dimethylglycine show diverse associations with cardiometabolic risk factors [1,2,3]. Low fasting plasma betaine and dimethylglycine (i.e.; a betaine demethylation product) predict incident diabetes [4]

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