Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Choline Deficiency”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,441 records · Page 80Linked to original sources
PubMed1985

Involvement of water-soluble vitamins in diseases of swine.

The various roles of the water-soluble vitamins (including choline and vitamin C) in diseases of swine are outlined. The most important role is in the prevention of deficiency disease; another important role is in relation to the immune response. Deficiency signs relating to each vitamin are described and the metabolism of each vitamin is outlined. Recent estimates of requirements are set out, together with suggestions on supplementation of practical diets for swine.

Animals↗
PubMed2003

Methyl deficiency causes reduction of the methyl-CpG-binding protein, MeCP2, in rat liver.

MeCP2 is a member of a family of proteins [methyl- (cytosine-guanine)CpG-binding proteins] that bind specifically to methylated DNA and induce chromatin remodeling and gene silencing. Dietary deficiency of folate, choline and methionine causes decreased tissue S-adenosylmethionine concentrations (methyl deficiency), global DNA hypomethylation, hepatic steatosis, cirrhosis and ultimately hepatic tumorigenesis in rodents. We investigated the effects of this diet on expression of MeCP2 during pre-neoplastic transformation of liver tissue. After 9 weeks, MeCP2 mRNA level was slightly higher in methyl-deficient rats compared with replete controls, while after 36 weeks, a difference in MeCP2 mRNA level was no longer observed. In contrast, MeCP2 protein level was reduced almost 2-fold in the deficient rats compared with replete controls at both 9 and 36 weeks. Conversely, a second methyl-CpG-binding protein, MBD2, showed increased levels of both message and protein at the two time points. Low MeCP2 protein in the deficient rats was associated with a low level of the co-repressor protein, Sin3a, at 36 weeks. Moreover, a known gene target of MeCP2, the tumor suppressor gene metallothionein-I, was over-expressed in the deficient rat livers at both 9 and 36 weeks, suggesting that reduction in MeCP2 may have functional consequences. Methyl deficiency also caused an increase in the ratio of long to short variants of MeCP2 transcripts. This finding suggests that reduced MeCP2 protein level is the result of a reduced rate of translation. Reduction of MeCP2 protein expression may influence the initiation and/or progression of hepatic cancer induced by methyl deficiency and may provide a useful marker of pre-neoplastic change.

Animals↗
PubMed1993

Choline: its role in the growth of filamentous fungi and the regulation of mycelial morphology.

Choline is an essential metabolite for the growth of filamentous fungi. It occurs most notably as a component of the major membrane phospholipid, phosphatidyl choline (lecithin), and fulfills a major role in sulphate metabolism in the form of choline-o-sulphate in many species. Choline is usually synthesised endogenously, but exogenous choline can also be taken up, either to compensate for metabolic deficiencies in choline-requiring mutants such as those of Aspergillus nidulans and Neurospora crassa, or as a normal function by species such as Fusarium graminearum which do not require added choline for growth. F. graminearum has a highly specific constitutive uptake system for this purpose. Recent studies have begun to indicate that choline also plays an important role in hyphal and mycelial morphology. Over a wide range of concentrations, choline influences mycelial morphology, apparently by controlling branch initiation. At high concentrations of added choline, branching is inhibited but specific growth rate is unaffected, leading to the production of rapidly extending, sparsely branched mycelia. Reduction of choline concentration allows a progressive increase in branching. Additionally, in choline-requiring mutants which have a very reduced content of choline, multiple tip-formation and apical branching occurs. Just prior to cessation of growth in choline-starved cultures of A. nidulans choline-requiring mutants, hyphal morphology changes due to a brief phase of unpolarised growth to produce spherical swellings called balloons, at or near hyphal apices. The precise mechanism by which choline affects fungal morphology is not yet known, although in A. nidulans it appears to be at least partially due to the influence of membrane composition on the synthesis of the hyphal wall polymer chitin. Several hypotheses for the possible mode of action of choline in affecting fungal morphology are discussed here.

Cell Membrane↗
PubMed1983

Tissue levels of S-adenosylmethionine and S-adenosylhomocysteine in rats fed methyl-deficient, amino acid-defined diets for one to five weeks.

The levels of S-adenosylmethionine (AdoMet) and of S-adenosylhomocysteine (AdoHcy) as well as the ratio of AdoMet/AdoHcy were determined in the liver, lungs, testes and kidneys of weanling male rats fed a commercial chow diet or 5 different amino acid-defined diets for 1-5 weeks. The amino acid-defined diets used were as follows: diet 1, supplemented with methionine, choline, folic acid and vitamin B12; diet 2, deficient in methionine and choline; diet 3, deficient in methionine alone; diet 4, deficient in choline alone; diet 5, deficient in methionine, choline, folic acid and vitamin B12. All methionine-deficient diets were supplemented with an equimolar dose of its metabolic precursor, homocystine. The animals were sacrificed after 1, 3 and 5 weeks of treatment. In animals fed either the chow diet or diet 1, liver was the organ found to contain the highest levels of AdoMet and AdoHcy. Similarly, in animals fed diet 1 or chow, the testes and lungs contained the lowest level of AdoMet, while the lungs contained the lowest levels of AdoHcy. In general, the tissue levels of AdoHcy and AdoMet in rats fed diet 1 were very similar to the corresponding values found in chow-fed rats. Diet 1 feeding, however, led to higher hepatic levels of AdoMet than did the administration of the chow diet. The administration of the methyl-deficient diets generally led to decreased hepatic AdoMet contents at 3 and 5 weeks; the methyl-deficient diets also led to increased AdoHcy contents and decreased AdoMet:AdoHcy ratios when compared with diet 1. Linear regression analysis showed a significant direct correlation between the observed hepatic AdoMet levels and the methyl content of the diet as well as an inverse correlation between hepatic AdoHcy levels and dietary methyl contents. Unlike liver, the lung and testes did not show any decrease in AdoMet content following feeding of the methyl-deficient diets. These tissues did show, however, early significant increases in AdoHcy contents and corresponding decreases in the ratios of AdoMet:AdoHcy. These changes were found to be proportional to the dietary methyl content. The renal contents of AdoMet, AdoHcy and the ratio of AdoMet/AdoHcy were unaffected by any of the diets administered except for diet 5. The administration of diet 5 to rats for 5 weeks led to a significant increase in renal AdoHcy. These results provide evidence indicating that dietary methyl insufficiency may exert its role in carcinogenesis through a decreased availability of AdoMet in vivo.

Animals↗
PubMed2006

An overview of evidence for a causal relationship between dietary availability of choline during development and cognitive function in offspring.

This review is part of a series intended for non-specialists that will provide an overview of evidence for causal relationships between micronutrient deficiencies and brain function. Here, we review 34 studies in rodents linking the availability of choline during gestation and perinatal development to neurological function or performance of offspring in cognitive and behavioral tests. Experimental designs, major results, and statistical criteria are summarized in Tables 1-4. Based on our reading of the literature, the evidence suggests that choline supplementation during development results in improved performance of offspring in cognitive or behavioral tests, and in changes in a variety of neurological functional indicators: (1) enhanced performance was observed, particularly on more difficult tasks; (2) increases (choline supplementation) or decreases (choline deficiency) were observed in electrophysiological responsiveness and size of neurons in offspring; and (3) supplementation resulted in some protection against adverse effects of several neurotoxic agents (including alcohol) in offspring. Discussion topics include methodological issues, such as the importance of independent replication, causal criteria, and uncertainties in interpreting test results.

Animals↗
PubMed1994

Modulation of expression of fos and Ha-ras oncogenes and ornithine decarboxylase activity in mammary gland and liver of young female rats by the absence of dietary lipotropes.

There is evidence that diets deficient in lipotropes [methionine, choline, pteroylmonoglutamic acid (folic acid), and cyanocobalamin (vitamin B12)] induce and enhance hepatocarcinogenesis. This research examined the extent to which dietary lipotropes modify cellular oncogene expression and ornithine decarboxylase activity in mammary gland and liver of rats. Eighteen female Sprague-Dawley rats (8 wk old) were fed 3 wk on one of three diets: 1) a control synthetic diet; 2) a methyl-deficient diet lacking choline, methionine, pteroylmonoglutamic acid, and cyanocobalamin; or 3) a diet supplemented with twice the amount of each lipotrope as in the control synthetic diet. The group fed the methyl-deficient diet gained less body weight than groups fed the control or methyl-supplemented diet. The group fed the methyl-deficient diet had approximately 5- and 11-fold greater fos transcription in mammary gland and liver, respectively, than did the control group. The expression of the Ha-ras gene in mammary gland and liver of the group fed the methyl-deficient diet was increased by 4- and 6-fold compared with that of the control. Ornithine decarboxylase activity, considered to be a developmental marker, was higher in liver and mammary gland of the group fed the methyl-deficient diet than in either the group fed control synthetic diet or the group fed the methyl-supplemented diet. The methyl-deficient diet may have caused activation of the transcription factor fos and thus the activation of the transcription regulatory complex, AP-1. In turn, AP-1 may regulate genes, such as ornithine decarboxylase, which are responsible for cell proliferation and differentiation.

Animals↗
PubMed1980

Lecithin in Parkinson's disease.

Pathological and biochemical evidence reviewed favours the hypothesis that the dementia seen in Parkinson's disease, particularly after long-term levodopa therapy, is akin to Alzheimer's disease. We postulate, in late Parkinson's disease, the development of a relative cholinergic deficiency due to the accelerated process of aging and the presence of neurofibrillary tangles (with choline acetyl transferase deficiency.) This process would be enhanced by the imbalance in favour of dopaminergic predominance caused by chronic levodopa therapy, and would partially explain the increase in dementia. As a test of this hypothesis we have given 10 levodopa-treated parkinsonian patients with dementia, a regimen of lecithin (average 20 gms/day). A clear improvement in Kohs block design test of constructive ability was noted with a decrease in the toxic symptoms of confusion, hallucinations and nightmares. In another study lecithin produced a decrease in levodopa-induced abnormal movements, but at the expense of motor performance. These preliminary investigations indicate that the progressive dementia of Parkinson's disease may not be irreversible.

Humans↗
PubMed1999

Interaction between dietary methionine and methyl donor intake on rat liver betaine-homocysteine methyltransferase gene expression and organization of the human gene.

We previously showed that rat liver betaine-homocysteine methyltransferase (BHMT) mRNA content and activity increased 4-fold when rats were fed a methionine-deficient diet containing adequate choline, compared with rats fed the same diet with control levels of methionine (Park, E. I., Renduchintala, M. S., and Garrow, T. A. (1997) J. Nutr. Biochem. 8, 541-545). A further 2-fold increase was observed in rats fed the methionine-deficient diet with supplemental betaine. The nutrition studies reported here were designed to determine whether other methyl donors would induce rat liver BHMT gene expression when added to a methionine-deficient diet and to define the relationship between the degree of methionine restriction and level of methyl donor intake on BHMT expression. Therefore, rats were fed amino acid-defined diets varying in methionine and methyl donor composition. The effect of diet on BHMT expression was evaluated using Northern, Western, and enzyme activity analyses. Similar to when betaine was added to a methionine-deficient diet, choline or sulfonium analogs of betaine induced BHMT expression. The diet-induced induction of hepatic BHMT activity was mediated by increases in the steady-state level of its mRNA and immunodetectable protein. Using methyl donor-free diets, we found that methionine restriction was required but alone not sufficient for the high induction of BHMT expression. Concomitant with methionine restriction, dietary methyl groups were required for high levels of BHMT induction, and a dose-dependent relationship was observed between methyl donor intake and BHMT induction. Furthermore, the severity of methionine restriction influenced the magnitude of BHMT induction. To study the molecular mechanisms that regulate the expression of BHMT, we have cloned the human BHMT gene. This gene spans about 20 kilobases of DNA and contains 8 exons and 7 introns. Using RNA isolated from human liver and hepatoma cells, a major transcriptional start site has been mapped using the 5' rapid amplification of cDNA ends technique, and this start site is 26 nucleotides downstream from a putative TATA box.

Animals↗
PubMedDate not supplied

Enhanced incidence of leg abnormalities in reovirus WVU 2937-infected chickens fed various dietary levels of selected vitamins.

Five experiments were conducted to evaluate the incidence of leg abnormalities of 4-, 6-, and 8-week-old reovirus WVU 2937-infected and uninfected chickens fed diets containing 20%, 100%, or 200% of the 1977 National Research Council nutrient requirements (NRC-77) of poultry for manganese, biotin, niacin, choline, or folic acid. Reovirus infection significantly elevated the incidence of leg abnormalities in the biotin-, niacin-, and folic-acid-deficient chickens and decreased the incidence of leg abnormalities in choline-deficient chickens. Reovirus-infected male chickens had a significantly greater incidence of leg abnormalities than reovirus-infected female chickens in the biotin, niacin, and folic acid studies. No sex differences in the incidence of leg abnormalities were observed in uninfected chickens. The incidence of leg abnormalities decreased with increasing dietary levels of biotin, niacin, choline, or folic acid in all chickens except reovirus-infected male chickens in the biotin study. In the manganese study, neither reovirus infection nor dietary level had any effect on the incidence of leg abnormalities in male or female chickens.

Age Factors↗
PubMed2003

Selection and characterization of the choline transport mutation suppressor from Torpedo electric lobe, CTL1.

The presumptive choline transporter, CTL1, was initially identified through functional complementation of a triple yeast mutant (ctr ise URA3delta) with deficiencies in both choline transport and choline neosynthesis under selective conditions that cause perturbations in membrane synthesis and growth. After transformation of these yeasts with a heterologous yeast expression library made from Torpedo electric lobe cDNAs, several colonies showed increased growth but only one clone increased the accumulation of external choline. The corresponding full-length cDNA was isolated and encodes a protein with 10 transmembrane domains. Northern analysis of Torpedo mRNA indicates that CTL1 is expressed at high levels in the spinal cord and brain. In Xenopus oocytes, Torpedo CTL1 expression was associated with the appearance of sodium independent high-affinity choline uptake. We propose that CTL1 plays a role in providing choline for membrane synthesis in the nervous system.

Animals↗
PubMed1976

Phosphorylation of mononucleotides and formation of cytidine 5'-diphosphate-choline and sugar nucleotides by respiration-deficient mutants of yeasts.

Respiration-deficient mutants (Rho-, petite) of Saccharomyces carlsbergensis were obtained by treatment with trypaflavin (euflavine). Dried cells of these mutants phosphorylated mononucleotides to their triphosphates and further formed not only cytidine 5'-diphosphate-choline, but also sugar nucleotides, such as uridine 5'-diphosphate-glucose, guanosine 5'-diphosphate-mannose, etc. The activities were the same or slightly greater than those of the wild strain. These results showed that energy (adenosine 5'-triphosphate) necessary for phosphorylation of mononucleotides was sufficiently supplied by the glycolysis system.

Acriflavine↗
PubMed1973

Regulation by dietary choline of hepatic fatty acid synthetase in the rat.

Fatty acid synthetase activity was measured in the high-speed supernatant fraction of liver homogenates from rats fed a semisynthetic diet low in lipotropic factors. If choline was omitted from the diet, a significant increase of fatty acid synthetase activity was observed after two feedings of the deficient diet. Compared with controls, the increase of fatty acid synthetase activity was of a magnitude that could account for the amount of triglyceride accumulating in the hepatic floating lipid fraction. Gas-liquid chromatographic analysis of the floating lipid triglycerides showed an increased content of palmitic acid due to choline deficiency; this increase could be predicted from the increased fatty acid synthetase activity and its known characteristic yield of palmitic acid.

Administration, Oral↗
PubMed1988

Galanin-like immunoreactivity is unchanged in Alzheimer's disease and Parkinson's disease dementia cerebral cortex.

Galanin is a recently isolated neuropeptide that is of particular interest in dementing disorders because of its known colocalization with choline acetyltransferase in magnocellular neurons of the basal nucleus of Meynert. These neurons degenerate in Alzheimer's disease, and there is a corresponding deficiency of cortical choline acetyltransferase activity. In the present study, galanin-like immunoreactivity was measured in the postmortem cerebral cortex and hippocampus of 10 controls and 14 patients who had had Alzheimer's disease. Significant reductions of choline acetyltransferase activity (50-60%) were found in all regions examined; however, there was no significant effect on concentrations of galanin-like immunoreactivity. Similar measurements were made in postmortem tissues of 12 control and 13 demented Parkinsonian patients who had had Alzheimer-type cortical pathology. Choline acetyltransferase activity was again significantly decreased in all regions examined but there were no significant reductions in galanin-like immunoreactivity. Experimental lesions of the fornix in rats produced parallel significantly correlated reductions of both choline acetyltransferase activity and galanin-like immunoreactivity in the hippocampus. Galanin-like immunoreactivity in the human hypothalamus consisted of two molecular-weight species on gel-permeation chromatography, and two forms were resolved by reverse-phase HPLC. The paradoxical preservation of galanin-like immunoreactivity, despite depletion of the activity of choline acetyltransferase, with which it is colocalized, is as yet unexplained. Recent studies have shown that galanin inhibits both acetylcholine release in the hippocampus and memory acquisition; therefore, preserved galanin may exacerbate the cholinergic and cognitive deficits that accompany dementia.

Aged↗
PubMed1977

Reduction of N-nitrosodiethylamine carcinogenesis in rats by lipotrope or amino acid supplementation of a marginally deficient diet.

In studies in this and other laboratories, induction of hepatocardinoma by several different chemical carcinogens was enhanced in rats fed diets deficient in lipotropes (choline, methionine, folic acid), amino acids, and niacin, and high in fat. In some cases, specific supplementation with lipotropes blocked carcinogenesis. In studies reported here, specific supplementation of a marginally deficient diet that enhanced carcinogenesis in rats, with the amino acids or lipotropes in which it was deficient, significantly decreased induction of hepatocarcinoma by N-nitrosodiethylamine. Niacin supplementation decreased hepatocarcinoma incidence only slight; the addition of beef fat to an adequate diet did not enhance tumor induction. Rats fed the amino acid- or lipotrope-supplemented diets had an increased incidence of hepatic hemangioendothelial sarcomas, compared to deficient rats or to rats fed the adequate control diet. Methionine was contained in both the amino acid and the lipotrope supplement and probably was responsible for reducing hepatocarcinoma incidence. Methionine has been found to have an anticarcinogenic effect in other studies and also to block the depletion of hepatic folate stores that is induced by N-nitrosodiethylamine. Interactions between carcinogens, S-adenosylmethionine, and folate may be significant in hepatic or other tissue carcinogenesis. One of more hepatic microsomal oxidases were depressed in rats fed any of the high-fat diets but were not correlated with tumor incidence.

Amino Acids↗
PubMed2002

The effects of diet, genetics and chemicals on toxicity and aberrant DNA methylation: an introduction.

In the early 1930s, the group of Banting and Best showed that the choline moiety of lecithin was responsible for the prevention of the fatty livers produced in pancreatectomized dogs treated with insulin. This was the first study linking abnormal methyl metabolism with disease. Since then, deficiencies of each of the four essential dietary sources of methyl groups (choline, methionine, vitamin B-12 and folic acid) have been associated with increased risk of a number of diseases. Choline-deficient diets were shown to enhance liver tumor formation in rats, and such diets frequently were found to lead to atherosclerosis. Although methionine deficiency per se was not extensively studied in vivo, its metabolic antagonist ethionine did cause liver cancer and pancreatic toxicity in rodents. Deficiencies of vitamin B-12 and of folic acid have long been shown to cause neurological disturbances and birth defects both in humans and in experimental animals. In 1969 inborn errors of metabolism leading to the accumulation of the demethylated metabolite of methionine, homocysteine, were proposed as contributing to the early onset of atherosclerosis. Before 1990, numerous studies described the abnormal methylation of DNA in tumors and transformed cells. Less frequently investigated, however, were the exogenous and endogenous agents leading to such abnormal methylation. These included genetic variants among rodent strains and the methyl-deficient diets that caused liver cancer. In addition, several chemicals, particularly carcinogens, were shown to alter DNA methylation. The possible links between chemically induced alterations in DNA methylation and development of other diseases were little explored. However, by 1990, a chain of causality had been established in experimental carcinogenesis linking dietary methyl deficiency with methyl insufficiency in vivo, as well as with the abnormal methylation of DNA and of specific genes. Also during this period, the diminished activity of the enzyme methylenetetrahydrofolate reductase (EC 1.5.1.20), which is responsible for the actual de novo synthesis of methyl groups, was shown to be associated with increased risk of developing atherosclerosis, neurological disorders and birth defects. The exponential rise in studies on methyl metabolism and DNA methylation since then enables us to examine here the extent to which the mechanisms by which abnormal methylation processes seem to exert their toxic effects in one disease may be applicable to other pathologies.

Animals↗
PubMed2006

Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid.

Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion, which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat model.

Absorptiometry, Photon↗