Choline: an essential nutrient for public health

Choline was officially recognized as an essential nutrient by the Institute of Medicine (IOM) in 1998. There is a significant variation in the dietary requirement for choline that can be explained by common genetic polymorphisms. Because of its wide-ranging roles in human metabolism, from cell structure to neurotransmitter synthesis, choline-deficiency is now thought to have an impact on diseases such as liver disease, atherosclerosis and possibly neurological disorders. Choline is found in a wide variety of foods. Egg yolks are the most concentrated source of choline in the American diet, providing 680 milligrams per 100 grams. Mean choline intakes for older children, men, women and pregnant women are far below the Adequate Intake established by the IOM. Given the importance of choline in a wide range of critical functions in the human body, coupled with less than optimal intakes among the population, dietary guidance should be developed to encourage the intake of choline-rich foods

Hepatic protein kinase C is not activated despite high intracellular 1,2-sn-diacylglycerol in obese Zucker rats

AbstractHigh intracellular 1,2,-sn-diacylglycerol (DAG) usually activates protein kinase C (PKC). In choline-deficient Fischer 344 rats, we previously showed that fatty liver was associated with elevated hepatic DAG and sustained activation of PKC. Steatosis is a sequelae of many liver toxins, and we wanted to determine whether fatty liver is always associated with accumulation of DAG with activation of PKC. Obese Zucker rats had 11-fold more triacylglycerol in their livers and 2-fold more DAG in their hepatic plasma membrane than did lean control Zucker rats. However, this increased diacylglycerol was not associated with translocation or activation of PKC in hepatic plasma membrane (activity in obese rats was 897 pmol/mg protein×min−1 vs. 780 pmol/mg protein×min−1 in lean rats). No differences in PKC isoform expression were detected between obese and lean rats. In additional studies, we found that choline deficiency in the Zucker rat did not result in activation of PKC in liver, unlike our earlier observations in the choline deficient Fischer rat. This dissociation between fatty liver, DAG accumulation and PKC activation in Zucker rats supports previous reports of abnormalities in PKC signaling in this strain of rats

Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load

Elevated concentrations of homocysteine in blood may be an independent risk factor for the development of atherosclerosis. Elevated homocysteine concentrations can be caused by decreased methylation of homocysteine to form methionine, as occurs in folate deficiency. A parallel pathway exists for methylation of homocysteine, in which choline, by way of betaine, is the methyl donor

Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not

Some humans fed a low-choline diet develop hepatosteatosis, liver and muscle damage, and lymphocyte apoptosis. The risk of developing such organ dysfunction is increased by the presence of single-nucleotide polymorphisms (SNPs) in genes involved in folate and choline metabolism

The betaine content of sweat from adolescent females

<p>Abstract</p> <p>Background</p> <p>This study was developed to establish whether betaine was present in the sweat of females and to determine any correlations with other sweat components.</p> <p>Methods</p> <p>Sweat patches were placed on eight trained adolescent Highland dancers (age = 13.6 ± 2.3 yr), who then participated in a dance class for 2 hours. Patches were removed, and the sweat recovered via centrifugation. The sweat was subsequently analyzed for betaine, choline, sodium, potassium, chloride, lactate, glucose, urea and ammonia.</p> <p>Results</p> <p>Betaine was present in the sweat of all subjects (232 ± 84 μmol·L^-1), which is higher than typically found in plasma. The concentration of several sweat components were correlated, in particular betaine with most other measured components.</p> <p>Conclusion</p> <p>Betaine, an osmoprotectant and methyl donor, is a component of sweat that may be lost from the body in significant amounts.</p

Choline deficiency increases lymphocyte apoptosis and DNA damage in humans

Whereas deficiency of the essential nutrient choline is associated with DNA damage and apoptosis in cell and rodent models, it has not been shown in humans

Phosphatidylethanolamine N -methyltransferase ( PEMT ) gene expression is induced by estrogen in human and mouse primary hepatocytes

Choline is an essential nutrient for humans, though some of the requirement can be met by endogenous synthesis catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). Premenopausal women are relatively resistant to choline deficiency compared with postmenopausal women and men. Studies in animals suggest that estrogen treatment can increase PEMT activity. In this study we investigated whether the PEMT gene is regulated by estrogen. PEMT transcription was increased in a dose-dependent manner when primary mouse and human hepatocytes were treated with 17-β-estradiol for 24 h. This increased message was associated with an increase in protein expression and enzyme activity. In addition, we report a region that contains a perfect estrogen response element (ERE) ∼7.5 kb from the transcription start site corresponding to transcript variants {"type":"entrez-nucleotide","attrs":{"text":"NM_007169","term_id":"22538481","term_text":"NM_007169"}}NM_007169 and NM-008819 of the human and murine PEMT genes, respectively, three imperfect EREs in evolutionarily conserved regions and multiple imperfect EREs in nonconserved regions in the putative promoter regions. We predict that both the mouse and human PEMT genes have three unique transcription start sites, which are indicative of either multiple promoters and/or alternative splicing. This study is the first to explore the underlying mechanism of why dietary requirements for choline vary with estrogen status in humans.—Resseguie, M., Song, J., Niculescu, M. D., da Costa, K., Randall, T. A., Zeisel, S. H. Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes

Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD)

Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes phosphatidylcholine synthesis. PEMT knockout mice have fatty livers, and it is possible that, in humans, nonalcoholic fatty liver disease (NAFLD) might be associated with PEMT gene polymorphisms. DNA samples from 59 humans without fatty liver and from 28 humans with NAFLD were genotyped for a single nucleotide polymorphism in exon 8 of PEMT which leads to a V175M substitution. V175M is a loss of function mutation, as determined by transiently transfecting McArdle-RH7777 cells with constructs of wildtype PEMT open reading frame or the V175M mutant. Met/Met at residue 175 (loss of function SNP) occurred in 67.9% of the NAFLD subjects and in only 40.7% of control subjects (p< 0.03). For the first time we report that a polymorphism of the human PEMT gene (V175M) is associated with diminished activity and may confer susceptibility to NAFLD

Regulation of Choline Deficiency Apoptosis by Epidermal Growth Factor in CWSV-1 Rat Hepatocytes

Previous studies show that acute choline deficiency (CD) triggers apoptosis in cultured rat hepatocytes (CWSV-1 cells). We demonstrate that prolonged EGF stimulation (10 ng/mL x 48 hrs) restores cell proliferation, as assessed by BrdU labeling, and protects cells from CD-induced apoptosis, as assessed by TUNEL labeling and cleavage of poly(ADP-ribose) polymerase. However, EGF rescue was not accompanied by restoration of depleted intracellular concentrations of choline, glycerphosphocholine, phosphocholine, or phosphatidylcholine. In contrast, we show that EGF stimulation blocks apoptosis by restoring mitochondrial membrane potential (ΔΨm), as determined using the potential-sensitive dye chloromethyl-X-rosamine, and by preventing the release and nuclear localization of cytochrome c. We investigated whether EGF rescue involves EGF receptor phosphorylation and activation of the down-stream cell survival factor Akt. Compared to cells in control medium (CT, 70 μmol choline x 48hrs), cells in CD medium (5 μmol choline) were less sensitive to EGF-induced (0–300 ng/mL x 5 min) receptor tyrosine phosphorylation. Compared to cells in CT medium, cells in CD medium treated with EGF (10 ng/mL x 5 min) exhibited higher levels of phosphatidylinositol 3-kinase (PI3K)-dependent phosphorylation of AktSer473. Inactivation of PI3K was sufficient to block EGF-stimulated activation of Akt, restoration of mitochondrial ΔΨm, and prevention of cytochrome c release. These studies indicate that stimulation with EGF activates a cell survival response against CD-apoptosis by restoring mitochondrial membrane potential and preventing cytochrome c release and nuclear translocation which are mediated by activation of Akt in hepatocytes

Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma

Background: Choline is essential for infant nutrition, and breast milk is a rich source of this nutrient. Common single nucleotide polymorphisms (SNPs) change dietary requirements for choline intake