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Zeisel choline

Yanyan Wang, Natalia Surzenko, Walter B Friday, Steven H Zeisel
Maternal diets low in choline, an essential nutrient, increase the risk of neural tube defects and lead to low performance on cognitive tests in children. However, the consequences of maternal dietary choline deficiency for the development and structural organization of the cerebral cortex remain unknown. In this study, we fed mouse dams either control (CT) or low-choline (LC) diets and investigated the effects of choline on cortical development in the offspring. As a result of a low choline supply between embryonic day (E)11 and E17 of gestation, the number of 2 types of cortical neural progenitor cells (NPCs)-radial glial cells and intermediate progenitor cells-was reduced in fetal brains (P< 0...
April 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jeffrey R Wozniak, Anita J Fuglestad, Judith K Eckerle, Birgit A Fink, Heather L Hoecker, Christopher J Boys, Joshua P Radke, Maria G Kroupina, Neely C Miller, Ann M Brearley, Steven H Zeisel, Michael K Georgieff
BACKGROUND: Fetal alcohol spectrum disorders (FASDs) are conditions characterized by physical anomalies, neurodevelopmental abnormalities, and neurocognitive deficits, including intellectual, executive, and memory deficits. There are no specific biological treatments for FASDs, but rodent models have shown that prenatal or postnatal choline supplementation reduces cognitive and behavioral deficits. Potential mechanisms include phospholipid production for axonal growth and myelination, acetylcholine enhancement, and epigenetic effects...
November 2015: American Journal of Clinical Nutrition
Xueqing Zhao, Steven Zeisel, Shucha Zhang
There is a growing interest in analyzing choline, betaine and their gut microbial metabolites including trimethylamine (TMA) and trimethylamine N-oxide (TMAO) in body fluids due to the high relevance of these compounds for human health and diseases. A stable isotope dilution (SID)-LC-MRM/MS assay was developed for the simultaneous determination of choline, betaine, TMA, TMAO and creatinine in human plasma and urine. The assay was validated using quality control (QC) plasma samples, spiked at low, medium and high levels...
June 17, 2015: Electrophoresis
Matt J Silver, Karen D Corbin, Garrett Hellenthal, Kerry-Ann da Costa, Paula Dominguez-Salas, Sophie E Moore, Jennifer Owen, Andrew M Prentice, Branwen J Hennig, Steven H Zeisel
Choline is an essential nutrient, and the amount needed in the diet is modulated by several factors. Given geographical differences in dietary choline intake and disparate frequencies of single-nucleotide polymorphisms (SNPs) in choline metabolism genes between ethnic groups, we tested the hypothesis that 3 SNPs that increase dependence on dietary choline would be under negative selection pressure in settings where choline intake is low: choline dehydrogenase (CHDH) rs12676, methylenetetrahydrofolate reductase 1 (MTHFD1) rs2236225, and phosphatidylethanolamine-N-methyltransferase (PEMT) rs12325817...
August 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Hiroyuki Tsuchiya, Kerry-Ann da Costa, Sangmin Lee, Barbara Renga, Hartmut Jaeschke, Zhihong Yang, Stephen J Orena, Michael J Goedken, Yuxia Zhang, Bo Kong, Margitta Lebofsky, Swetha Rudraiah, Rana Smalling, Grace Guo, Stefano Fiorucci, Steven H Zeisel, Li Wang
BACKGROUND & AIMS: Hyperhomocysteinemia is often associated with liver and metabolic diseases. We studied nuclear receptors that mediate oscillatory control of homocysteine homeostasis in mice. METHODS: We studied mice with disruptions in Nr0b2 (called small heterodimer partner [SHP]-null mice), betaine-homocysteine S-methyltransferase (Bhmt), or both genes (BHMT-null/SHP-null mice), along with mice with wild-type copies of these genes (controls). Hyperhomocysteinemia was induced by feeding mice alcohol (National Institute on Alcohol Abuse and Alcoholism binge model) or chow diets along with water containing 0...
May 2015: Gastroenterology
Laila C Schenkel, Ratnesh K Singh, Vera Michel, Steven H Zeisel, Kerry-Ann da Costa, Amy R Johnson, Harvey S Mudd, Marica Bakovic
Fibroblasts from a patient with postural orthostatic tachycardia syndrome (POTS), who presented with low plasma choline and betaine, were studied to determine the metabolic characteristics of the choline deficiency. Choline is required for the synthesis of the phospholipid phosphatidylcholine (PC) and for betaine, an important osmoregulator. Here, choline transport, lipid homeostasis, and mitochondria function were analyzed in skin fibroblasts from POTS and compared with control cells. The choline transporter-like protein 1/solute carrier 44A1 (CTL1/SLC44A1) and mRNA expression were 2-3 times lower in POTS fibroblasts, and choline uptake was reduced 60% (P < 0...
May 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Carolyn A Miller, Karen D Corbin, Kerry-Ann da Costa, Shucha Zhang, Xueqing Zhao, Joseph A Galanko, Tondra Blevins, Brian J Bennett, Annalouise O'Connor, Steven H Zeisel
BACKGROUND: It is important to understand whether eating eggs, which are a major source of dietary choline, results in increased exposure to trimethylamine-N-oxide (TMAO), which is purported to be a risk factor for developing heart disease. OBJECTIVE: We determined whether humans eating eggs generate TMAO and, if so, whether there is an associated increase in a marker for inflammation [ie, high-sensitivity C-reactive protein (hsCRP)] or increased oxidation of low-density lipoprotein (LDL)...
September 2014: American Journal of Clinical Nutrition
Kerry-Ann da Costa, Karen D Corbin, Mihai D Niculescu, Joseph A Galanko, Steven H Zeisel
Effect alleles (alleles with a polymorphism that is associated with the effect being measured) in a small number of single-nucleotide polymorphisms (SNPs) are known to influence the dietary requirement for choline. In this study, we examined a much larger number of SNPs (n=200) in 10 genes related to choline metabolism for associations with development of organ dysfunction (liver or muscle) when 79 humans were fed a low-choline diet. We confirmed that effect alleles in SNPs such as the C allele of PEMT rs12325817 increase the risk of developing organ dysfunction in women when they consume a diet low in choline, and we identified novel effect alleles, such as the C allele of CHKA SNP rs7928739, that alter dietary choline requirements...
July 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jeffrey R Wozniak, Anita J Fuglestad, Judith K Eckerle, Maria G Kroupina, Neely C Miller, Christopher J Boys, Ann M Brearley, Birgit A Fink, Heather L Hoecker, Steven H Zeisel, Michael K Georgieff
There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events...
November 2013: Nutrition Research
Anita J Fuglestad, Birgit A Fink, Judith K Eckerle, Christopher J Boys, Heather L Hoecker, Maria G Kroupina, Steven H Zeisel, Michael K Georgieff, Jeffrey R Wozniak
This study evaluated dietary intake in children with fetal alcohol spectrum disorders (FASD). Pre-clinical research suggests that nutrient supplementation may attenuate cognitive and behavioral deficits in FASD. Currently, the dietary adequacy of essential nutrients in children with FASD is unknown. Dietary data were collected as part of a randomized, double-blind controlled trial of choline supplementation in FASD. Participants included 31 children with FASD, ages 2.5-4.9 years at enrollment. Dietary intake data was collected three times during the nine-month study via interview-administered 24-hour recalls with the Automated Self-Administered 24-hour Recall...
September 2013: Neurotoxicology and Teratology
Steven H Zeisel
Women, during pregnancy and lactation, should eat foods that contain adequate amounts of choline. A mother delivers large amounts of choline across the placenta to the fetus, and after birth she delivers large amounts of choline in milk to the infant; this greatly increases the demand on the choline stores of the mother. Adequate intake of dietary choline may be important for optimal fetal outcome (birth defects, brain development) and for maternal liver and placental function. Diets in many low income countries and in approximately one-fourth of women in high income countries, like the United States, may be too low in choline content...
2013: International Journal of Women's Health
Paula Dominguez-Salas, Sophie E Moore, Darren Cole, Kerry-Ann da Costa, Sharon E Cox, Roger A Dyer, Anthony J C Fulford, Sheila M Innis, Robert A Waterland, Steven H Zeisel, Andrew M Prentice, Branwen J Hennig
BACKGROUND: Animal models show that periconceptional supplementation with folic acid, vitamin B-12, choline, and betaine can induce differences in offspring phenotype mediated by epigenetic changes in DNA. In humans, altered DNA methylation patterns have been observed in offspring whose mothers were exposed to famine or who conceived in the Gambian rainy season. OBJECTIVE: The objective was to understand the seasonality of DNA methylation patterns in rural Gambian women...
June 2013: American Journal of Clinical Nutrition
Mihai G Mehedint, Steven H Zeisel
PURPOSE OF REVIEW: Humans eating diets low in choline develop fatty liver and liver damage. Rodents fed choline-methionine-deficient diets not only develop fatty liver, but also progress to develop fibrosis and hepatocarcinoma. This review focuses on the role of choline in liver function, with special emphasis on the epigenetic mechanisms of action. RECENT FINDINGS: Dietary intake of methyl donors like choline influences the methylation of DNA and histones, thereby altering the epigenetic regulation of gene expression...
May 2013: Current Opinion in Clinical Nutrition and Metabolic Care
Karen D Corbin, Manal F Abdelmalek, Melanie D Spencer, Kerry-Ann da Costa, Joseph A Galanko, Wei Sha, Ayako Suzuki, Cynthia D Guy, Diana M Cardona, Alfonso Torquati, Anna Mae Diehl, Steven H Zeisel
Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleotide polymorphisms (SNPs) across genes of choline/1-carbon metabolism and functionally related pathways increase susceptibility to developing hepatic steatosis. In biopsy-characterized cases of nonalcoholic fatty liver disease and controls, we assessed 260 SNPs across 21 genes in choline/1-carbon metabolism...
April 2013: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Steven H Zeisel
In 1850, Theodore Gobley, working in Paris, described a substance, 'lecithine', which he named after the Greek 'lekithos' for egg yolk. Adolph Strecker noted in 1862 that when lecithin from bile was heated, it generated a new nitrogenous chemical that he named 'choline'. Three years later, Oscar Liebreich identified a new substance, 'neurine', in the brain. After a period of confusion, neurine and choline were found to be the same molecule, and the name choline was adapted. Lecithin was eventually characterized chemically as being phosphatidylcholine...
2012: Annals of Nutrition & Metabolism
Carol L Cheatham, Barbara Davis Goldman, Leslie M Fischer, Kerry-Ann da Costa, J Steven Reznick, Steven H Zeisel
BACKGROUND: Choline is essential for fetal brain development, and it is not known whether a typical American diet contains enough choline to ensure optimal brain development. OBJECTIVE: The study was undertaken to determine whether supplementing pregnant women with phosphatidylcholine (the main dietary source of choline) improves the cognitive abilities of their offspring. DESIGN: In a double-blind, randomized controlled trial, 140 pregnant women were randomly assigned to receive supplemental phosphatidylcholine (750 mg) or a placebo (corn oil) from 18 wk gestation through 90 d postpartum...
December 2012: American Journal of Clinical Nutrition
Steven H Zeisel
There are multiple identified mechanisms involved in energy metabolism, insulin resistance and adiposity, but there are here-to-fore unsuspected metabolic factors that also influence these processes. Studies in animal models suggest important links between choline/1-carbon metabolism and energy homeostasis. Rodents fed choline deficient diets become hypermetabolic. Mice with deletions in one of several different genes of choline metabolism have phenotypes that include increased metabolic rate, decreased body fat/lean mass ratio, increased insulin sensitivity, decreased ATP production by mitochondria, or decreased weight gain on a high fat diet...
March 1, 2013: Clinical Chemistry and Laboratory Medicine: CCLM
Erin L Richman, Stacey A Kenfield, Meir J Stampfer, Edward L Giovannucci, Steven H Zeisel, Walter C Willett, June M Chan
BACKGROUND: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline-a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. OBJECTIVE: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer...
October 2012: American Journal of Clinical Nutrition
Karen D Corbin, Steven H Zeisel
Advances in nutrigenetics and nutrigenomics have been instrumental in demonstrating that nutrient requirements vary among individuals. This is exemplified by studies of the nutrient choline, in which gender, single-nucleotide polymorphisms, estrogen status, and gut microbiome composition have been shown to influence its optimal intake level. Choline is an essential nutrient with a wide range of biological functions, and current studies are aimed at refining our understanding of its requirements and, importantly, on defining the molecular mechanisms that mediate its effects in instances of suboptimal dietary intake...
2012: Progress in Molecular Biology and Translational Science
Steven H Zeisel
One of the underlying mechanisms for metabolic individuality is genetic variation. Single nucleotide polymorphisms (SNPs) in genes of metabolic pathways can create metabolic inefficiencies that alter the dietary requirement for, and responses to, nutrients. These SNPs can be detected using genetic profiling and the metabolic inefficiencies they cause can be detected using metabolomic profiling. Studies on the human dietary requirement for choline illustrate how useful these new approaches can be, as this requirement is influenced by SNPs in genes of choline and folate metabolism...
2012: Annals of Nutrition & Metabolism
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