Choline, Other Methyl-Donors and Epigenetics

Zeisel, Steven H.

doi:10.3390/nu9050445

Cited by 195 publications

(149 citation statements)

References 98 publications

(118 reference statements)

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“…). This is perhaps not surprising given the known role of choline as a methyl donor and regulator of epigenetic changes in many tissues (Zeisel, ). However, choline's effects are not necessarily restricted to these brain regions.…”

Section: Discussionmentioning

confidence: 97%

Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

Akison

Kuo

Reid

et al. 2018

Alcoholism Clin & Exp Res

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Prenatal alcohol exposure results in cognitive, behavioral, and neurological deficits in offspring. There is an urgent need for safe and effective treatments to overcome these effects. Maternal choline supplementation has been identified as a potential intervention. Our objective was to review preclinical and clinical studies using choline supplementation in known cases of fetal alcohol exposure to determine its effectiveness in ameliorating deficits in offspring. A systematic search of 6 electronic databases was conducted and studies selected by reviewing titles/abstracts against specific inclusion/exclusion criteria. Study characteristics, population demographics, alcohol exposure, and intervention methods were tabulated, and quality of reporting was assessed. Data on cognitive, behavioral, and neurological outcomes were extracted and tabulated. Quantitative analysis was performed to determine treatment effects for individual study outcomes. A total of 189 studies were retrieved following duplicate removal. Of these, 22 studies (2 randomized controlled trials, 2 prospective cohort studies, and 18 preclinical studies) met the full inclusion/exclusion criteria. Choline interventions were administered at different times relative to alcohol exposure, impacting on their success to prevent deficits for specific outcomes. Only 1 clinical study showed significant improvements in information processing in 6-month-old infants from mothers treated with choline during pregnancy. Preclinical studies showed significant amelioration of deficits due to prenatal alcohol exposure across a wide variety of outcomes, including epigenetic/molecular changes, gross motor, memory, and executive function. This review suggests that choline supplementation has the potential to ameliorate specific behavioral, neurological, and cognitive deficits in offspring caused by fetal alcohol exposure, at least in preclinical studies. As only 1 clinical study has shown benefit, we recommend more clinical trials be undertaken to assess the effectiveness of choline in preventing deficits across a wider range of cognitive domains in children.

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Section: Discussionmentioning

confidence: 97%

Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

Akison

Kuo

Reid

et al. 2018

Alcoholism Clin & Exp Res

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“…One of the important functions of choline is to serve as a methyl-group donor used for the synthesis of Ado-Met (1). AdoMet concentrations are diminished, and S-adenosylhomocysteine (AdoHcy) concentrations are increased in animals consuming LC diets (33,34); the ratio of these 2 metabolites determines the rate of methylation reactions (35,36). Therefore, we assayed AdoMet and AdoHcy concentrations in AC and LC E17 brains.…”

Section: Choline-mediated Changes In Methylation Potential Regulate Ementioning

confidence: 99%

MicroRNA‐129‐5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex

et al. 2018

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Choline availability modulates neurogenesis and cerebral cortex development through the regulation of neural progenitor cell (NPC) proliferative and differentiation capacity. In this study, we demonstrated that cortical NPC self‐renewal is controlled by choline via the expression of a microRNA (miR‐129‐5p), whose role in the developing brain has not been examined, and which, in turn, inhibits synthesis of the epidermal growth factor receptor (EGFR) protein. Specifically, we found that low choline (LC) availability led to the upregulation of miR‐129‐5p expression in cortical NPCs in vitro and in vivo, causing the downregulation of EGFR and thereby disrupting NPC self‐renewal and cortical neurogenesis. Furthermore, in response to LC availability, methylation potential (the S‐adenosylmethionine:S‐adenosylhomocysteine ratio) in the developing brain was reduced. Restoring methylation potential in LC cortical NPCs led to the re‐establishment of normal miR‐129‐5p expression. We concluded that inhibiting miR‐129‐5p function and restoring EGFR protein levels in vivo is sufficient to reverse LC‐induced defects in cortical NPC self‐renewal. For the first time, to our knowledge, we have identified the molecular links that explain how a change in the availability of the diet metabolite choline impacts the essential cellular processes underlying brain development.—Trujillo‐Gonzalez, I., Wang, Y., Friday, W. B., Vickers, K. C., Toth, C. L., Molina‐Torres, L., Surzenko, N., Zeisel, S. H. MicroRNA‐129‐5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex. FASEB J. 33, 3601–3612 (2019). http://www.fasebj.org

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“…It is clear that the nonuniform changes in the plasma TAG lipidome develop in response to MDS. These changes may be due to the ability of methyl donors to modulate DNA methylation of lipogenic genes, including fatty acid synthase, sterol regulatory element-binding protein, and acylglycerophosphate acyltransferase (Dahlhoff et al, 2014;Zeisel, 2017). Future research will need to optimize the ability of MDS to increase the hepatic secretion of all TAG, because lowering hepatic lipid content has the potential to improve gluconeogenesis and mitochondrial β-oxidation (Rukkwamsuk et al, 1999;Litherland et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Methyl donor supplementation suppresses the progression of liver lipid accumulation while modifying the plasma triacylglycerol lipidome in periparturient Holstein dairy cows

Zang

Samii

Myers

et al. 2019

Journal of Dairy Science

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Co-supplementation of methyl donors may lower hepatic lipid content in transition cows. To define the ability of methyl donor supplementation (MDS) to reduce hepatic lipid content and modify the plasma lipidome, 30 multiparous Holstein cows (2.04 ± 0.69 lactations; 689 ± 58 kg of body weight; 3.48 ± 0.10 units of body condition score) were fed a ration with or without rumen-protected methyl donors (22 g/d of Met, 10 g/d of choline chloride, 3 g/d of betaine, 96 mg/d of riboflavin, and 1.4 mg/d of vitamin B 12 ) from d −28 before expected calving through d 14 postpartum. Cows were randomly enrolled based on predefined selection criteria (body condition score and parity). Base diets without MDS were formulated for gestation (15.4% crude protein with a predicted Lys-to-Met ratio of 3.25; 1.44 Mcal of net energy for lactation/ kg of dry matter) and lactation (16.6% crude protein with a predicted Lys-to-Met ratio of 3.36; 1.64 Mcal of net energy for lactation/kg of dry matter). Blood sampling occurred from d −28 relative to expected calving through d 14 postpartum. Liver tissue was biopsied at d −28 relative to expected calving and on d 5 and 14 postpartum. In addition to routine analyses, serum AA concentrations on d 10 and 12 were quantified using mass spectrometry. Plasma triacylglycerol (TAG) and cholesteryl esters (CE) were qualitatively measured using time-of-flight mass spectrometry. Data were analyzed using a mixed model with repeated measures. Dry matter intake and milk yield were not modified by MDS. The transition from d −28 relative to expected parturition to d 14 postpartum was characterized by increased plasma fatty acid (0.15 to 0.71 mmol/L) and β-hydroxybutyrate (0.34 to 0.43 mmol/L) levels and liver lipid content (3.91 to 9.16%). Methyl donor supplementation increased the serum Met level by 26% and decreased the serum Lys-to-Met ratio by 21% on d 10 and 12, respectively. Moreover, the increase in hepatic lipid content from d 5 through 14 postpartum was suppressed with MDS relative to control (3.57 vs. −0.29%). Dietary MDS modified the TAG and CE lipidome. For example, MDS increased plasma TAG 46:3 (carbon number: double bond) by 116% relative to control cows on d 5 postpartum. Moreover, MDS tended to increase plasma CE 34:6. In contrast, MDS lowered plasma TAG 54:8 by 39% relative to control cows on d 5 postpartum. We concluded that in the absence of gains in dry matter intake and milk and milk protein yields, dietary MDS slows the progression of hepatic lipid accumulation and modifies the plasma TAG lipidome in transition cows.

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Choline, Other Methyl-Donors and Epigenetics

Cited by 195 publications

References 98 publications

Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

Effect of Choline Supplementation on Neurological, Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

MicroRNA‐129‐5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex

Methyl donor supplementation suppresses the progression of liver lipid accumulation while modifying the plasma triacylglycerol lipidome in periparturient Holstein dairy cows

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