Effect of choline deficiency on <i>S</i>-adenosylmethionine and methionine concentrations in rat liver

Zeisel, Steven H.; Zola, T; daCosta, Kerry Ann; Pomfret, Elizabeth A.

doi:10.1042/bj2590725

Cited by 101 publications

(60 citation statements)

References 36 publications

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“…The close interrelationship of choline, folic acid, vitamin B 12 , and methionine metabolism intersects at the formation of methionine from homocysteine. Methionine can be formed through 2 pathways: from homocysteine, using methyl groups donated by methyltetrahydrofolate, or from methyl groups derived from betaine (which is derived from choline).…”

Section: Choline Folic Acid and Methionine Metabolism Are Relatedmentioning

confidence: 99%

The fetal origins of memory: The role of dietary choline in optimal brain development

Zeisel

2006

The Journal of Pediatrics

195

140

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Fetal nutrition sets the stage for organ function in later life. In this review we discuss the fetal and neonatal origins of brain function. Numerous research observations point to the importance of choline for the developing fetus and neonate. This essential nutrient is involved in 1-carbon metabolism and is the precursor for many important compounds, including phospholipids, acetylcholine, and the methyl donor betaine. Dietary intake of choline by the pregnant mother and later by the infant directly affects brain development and results in permanent changes in brain function. In rodents, perinatal supplementation of choline enhances memory and learning functions, changes that endure across the lifespan. Conversely, choline deficiency during these sensitive periods results in memory and cognitive deficits that also persist. Furthermore, recent studies suggest that perinatal choline supplementation can reduce the behavioral effects of prenatal stress and the cognitive effects of prenatal alcohol exposure in offspring. The likely mechanism for these effects of choline involves DNA methylation, altered gene expression, and associated changes in stem cell proliferation and differentiation. The currently available animal data on choline and hippocampal development are compelling, but studies are needed to detrermine whether the same is true in humans.There is a growing body of evidence indicating that fetal and perinatal nutrition and growth influence organ function in adult life (eg, blood pressure, 1 heart disease, 2 diabetes 3 ). Evidence also indicates that fetal and perinatal nutrition influence brain function in later life. Iron, 4 zinc, 5 and folate 6 nutriture in the fetus have been shown to alter brain development, and there is compelling data showing that another important nutrient, choline, is essential for brain formation. The human requirement for choline was officially recognized with the establishment of adequate intake recommendations by the Institute of Medicine in 1998 7 (adequate intake for infants age 0 to 6 months, 18 mg/kg/day). Choline is required for the structural integrity and signaling functions of cell membranes, methyl group metabolism, and neurotransmitter synthesis. 8 Some of the choline needed to sustain normal organ function is synthesized de novo, mainly in the liver, 9 when phosphatidylethanolamine is methylated by phosphatidylethanolamine N-methyltransferase (PEMT) to form phosphatidylcholine. However, this mechanism does not always meet the demands for choline, and humans eating diets deficient in choline develop fatty liver, liver damage, and muscle damage. 10,11 In this review, the main focus is on choline's role in brain development and function during the perinatal period.

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Section: Choline Folic Acid and Methionine Metabolism Are Relatedmentioning

confidence: 99%

The fetal origins of memory: The role of dietary choline in optimal brain development

Zeisel

2006

The Journal of Pediatrics

195

140

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“…1), dietary methyl group donors such as methionine and choline (or choline metabolite betaine) are of utmost importance in regulating these processes. During choline deficiency, hepatic SAM concentrations are decreased by as much as 50% [45][46][47][48]. Animals fed diets deficient in methyl donors (choline and methionine) have hypomethylated DNA [49][50][51].…”

Section: Animal Studiesmentioning

confidence: 99%

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

Duric

Sivanesan

Bakovic

2012

Euro J Lipid Sci & Tech

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Non‐alcoholic fatty liver disease (NAFLD) is the most common liver condition in the developed world and may progress to more severe forms of disease such as cirrhosis or liver cancer. Thus, steps taken to reduce its prevalence through preventative nutritional approaches such as functional foods and nutraceuticals (FFN) should be pursued. It is well known that certain lipotropic nutrients such as choline and metabolites betaine and phosphatidylcholine (PC; lecithin) could prevent or alleviate fatty liver through a variety of mechanisms, including increased hepatic VLDL secretion. Animal and human studies have demonstrated clear protective effects of choline, betaine and PC for NAFLD as well as possible roles in CVD prevention from epidemiological data. Currently, choline consumption is below dietary recommendations due in large part to a general lack of understanding regarding the importance of this nutrient for human health. As lecithin is commonly added (in small amounts) in many processed foods due to its functional capabilities, it is projected that increasing its abundance in the food supply and increasing consumer education and acceptance of lecithin‐based functional foods and nutraceuticals may represent a progressive step towards preventing liver and whole‐body metabolic pathologies in many areas of the world.

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“…Because in mammals one-carbon metabolism is dependent on the dietary supply of methyl group donors and cofactors (16), folate, methionine, vitamin B 12 , and choline can influence levels of SAM and SAH in the cell. Indeed, rats ingesting a choline-deficient diet have diminished tissue concentrations of methionine and SAM (17)(18)(19). Because SAM is a donor of methyl groups for most biological methylations, SAM availability can affect DNA…”

mentioning

confidence: 99%

Gestational Choline Deficiency Causes Global and Igf2 Gene DNA Hypermethylation by Up-regulation of Dnmt1 Expression

Kovacheva

Mellott

Davison

et al. 2007

Journal of Biological Chemistry

211

191

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During gestation there is a high demand for the essential nutrient choline. Adult rats supplemented with choline during embryonic days (E) 11-17 have improved memory performance and do not exhibit age-related memory decline, whereas prenatally choline-deficient animals have memory deficits. Choline, via betaine, provides methyl groups for the production of S-adenosylmethionine, a substrate of DNA methyltransferases (DNMTs). We describe an apparently adaptive epigenomic response to varied gestational choline supply in rat fetal liver and brain. S-Adenosylmethionine levels increased in both organs of E17 fetuses whose mothers consumed a choline-supplemented diet. Surprisingly, global DNA methylation increased in choline-deficient animals, and this was accompanied by overexpression of Dnmt1 mRNA. Previous studies showed that the prenatal choline supply affects the expression of multiple genes, including insulin-like growth factor 2 (Igf2), whose expression is regulated in a DNA methylation-dependent manner. The differentially methylated region 2 of Igf2 was hypermethylated in the liver of E17 choline-deficient fetuses, and this as well as Igf2 mRNA levels correlated with the expression of Dnmt1 and with hypomethylation of a regulatory CpG within the Dnmt1 locus. Moreover, mRNA expression of brain and liver Dnmt3a and methyl CpG-binding domain 2 (Mbd2) protein as well as cerebral Dnmt3l was inversely correlated to the intake of choline. Thus, choline deficiency modulates fetal DNA methylation machinery in a complex fashion that includes hypomethylation of the regulatory CpGs within the Dnmt1 gene, leading to its overexpression and the resultant increased global and gene-specific (e.g. Igf2) DNA methylation. These epigenomic responses to gestational choline supply may initiate the long term developmental changes observed in rats exposed to varied choline intake in utero.An adequate supply of essential nutrients involved in the metabolism of methyl groups, including folic acid, vitamin B 12 , and choline, is central for normal development of the fetus. This is perhaps best exemplified by the discovery that the dietary supply of folic acid, a vitamin that acts as a coenzyme in one-carbon transfer pathways, during the periconceptual period is critical in prevention of neural tube defects (1). Studies in animal models (2-5) as well as recent epidemiological investigations in humans (6) indicate that choline intake during gestation is particularly important for the normal development and function of the central nervous system. In a frequently used experimental model that employs offspring of pregnant rats or mice consuming diets of varying choline content during the 7-day period of the second half of gestation (embryonic days E11-17), prenatal choline deficiency causes deficits in certain memory tasks (7), whereas prenatal choline supplementation leads to enhanced memory and attention and prevents agerelated memory decline (7-13). These behavioral changes are accompanied by electrophysiological, neuroanatomical, and neuro...

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Effect of choline deficiency on S-adenosylmethionine and methionine concentrations in rat liver

Cited by 101 publications

References 36 publications

The fetal origins of memory: The role of dietary choline in optimal brain development

The fetal origins of memory: The role of dietary choline in optimal brain development

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

Gestational Choline Deficiency Causes Global and Igf2 Gene DNA Hypermethylation by Up-regulation of Dnmt1 Expression

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