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PubMed1987

Choline biosynthesis in sheep. Evidence for extrahepatic synthesis.

1. Choline production by various tissues of the sheep was measured by determining venous and arterial free choline concentrations in blood samples taken from various vessels in conscious multicannulated sheep. 2. Significant production of free choline occurred in the upper and lower body regions, and specifically in the heart, brain and hind-limb muscles of sheep, but there was no significant uptake or output of phosphatidylcholine across these tissues, as determined by arterio-venous differences. 3. In contrast, in the rat there were no significant arterio-venous differences in the concentrations of free choline or phosphatidylcholine across the hind-body. 4. Synthesis of phosphatidylcholine from endogenous phosphatidylethanolamine and S-adenosyl-L-[methyl-14C]methionine was measured in experiments in vitro using microsomal preparations from a variety of sheep and rat tissues. 5. The biosynthetic activity was highest in liver from sheep and rats, although the activity in sheep microsomal preparations was about one-quarter of that in rat microsomal preparations. 6. Microsomal preparations from sheep lung, kidney, gut epithelium, brain, heart and skeletal muscles also showed considerable biosynthetic activity, but in the rat the activity was virtually confined to the liver. 7. Overall, the results show a significant production of choline in extrahepatic tissues of the sheep, with skeletal muscle contributing some 60% of this extrahepatic activity. Thus the extrahepatic production of choline in the sheep, together with the extensive reutilization of bile choline, can explain the maintenance of the large endogenous body pool of choline in this species.

Animals↗
PubMed1995

Phorbol ester stimulates choline uptake in Swiss 3T3 fibroblasts following introduction of the gene encoding protein kinase C alpha.

Phorbol 12-myristate 13-acetate (PMA) stimulated radiolabelled choline uptake and incorporation into phosphatidylcholine (PtdCho) in a time- and concentration-dependent manner in wild-type NIH 3T3 fibroblasts. The accumulation of labelled choline induced by PMA was paralled by an increase in choline mass. The results implicate protein kinase C (PKC) in the regulation of choline uptake. In order to address the PKC-subtype specificity of this response, a study was undertaken in Swiss 3T3 fibroblast cells, which normally express very low levels of PKC alpha. A retroviral expression system was used to introduce the genes for PKC alpha and neomycin resistance (used for selection) into the cells. Two resulting lines expressed PKC alpha at levels that were 20-fold higher than those found in the control (neomycin-resistant) line, or in the wild-type cells. In control Swiss 3T3 fibroblasts, 1 microM PMA elevated choline levels by only 30%, whereas, in Swiss 3T3 cell lines that stably over-expressed PKC alpha, PMA caused a 5-fold enhancement in [14C]choline accumulation. This concentration of PMA significantly increased [14C]PtdCho levels in both control and PKC alpha-over-expressing lines, although the effect in the latter was significantly greater. The effects of PMA were inhibited by the PKC antagonist sphingosine. These results implicate PKC alpha in the regulation of choline accumulation and phospholipid synthesis in fibroblasts. Although additional PKC subtypes appear to participate in the control of PtdCho synthesis in these cells, PMA-stimulated choline uptake in Swiss 3T3 fibroblasts is almost entirely dependent on the presence of PKC alpha.

3T3 Cells↗
PubMed1991

Abnormal erythrocyte choline transport in patients with chronic renal failure.

1. Erythrocyte choline transport has been studied in nine patients on maintenance haemodialysis for chronic renal failure, six patients on continuous ambulatory peritoneal dialysis, 31 patients with renal transplants and in nine normal control subjects. 2. The mean maximum rate of choline influx (Vmax., measured at an extracellular choline concentration of 250 mumol/l) was 66.7 (SD 14.1) mumol h-1 l-1 cells in patients on haemodialysis, 87.8 (SD 18.5) mumol h-1 l-1 cells in patients on continuous ambulatory peritoneal dialysis and 30.5 (SD 4.9) mumol h-1 l-1 cells in control subjects. The increase in choline flux in patients on haemodialysis and patients on continuous ambulatory peritoneal dialysis compared with control subjects was highly significant (P less than 0.001). 3. Renal transplant patients showed variable values for the Vmax. of choline influx (range 17.7-71.7 mumol h-1 l-1 cells). The values showed a significant negative correlation with creatinine clearance and this correlation correctly extrapolated to the maximum choline flux in normal subjects and in patients on dialysis. 4. The kinetics of choline transport have been studied in erythrocytes of patients on haemodialysis and control subjects in 'zero-trans' conditions after depletion of intracellular choline. The mean Vmax. in these conditions was 38.4 (SD 4.6) mumol h-1 l-1 cells in patients on haemodialysis compared with 14.2 (SD 3.7) mumol h-1 l-1 cells in control subjects. The mean Km under 'zero-trans' conditions was 19.4 (SD 2.4) mumol/l in patients on haemodialysis and 7.4 (SD 1.4) mumol/l in control subjects. These differences were significant (P less than 0.001).

Biological Transport↗
PubMed2001

The transfer of choline from the host to the bacterial cell surface requires glpQ in Haemophilus influenzae.

Haemophilus influenzae incorporates choline obtained from environmental sources onto its lipopolysaccharide as phosphorylcholine (ChoP). The decoration of the bacterial surface with ChoP contributes to pathogenesis by allowing for mimicry of the host. As the main reservoir for choline in the host is phosphatidylcholine, we tested whether other choline-containing molecules associated with eukaryotic membranes could provide an alternative source of choline. H. influenzae was able to use glycerophosphorylcholine (GPC), an abundant degradation product of phospholipids, as efficiently as free choline. Utilization of GPC required glpQ, which expresses an enzyme with glycerophosphodiester phosphodiesterase activity. In the absence of free choline, this gene was required for adherent H. influenzae to obtain choline directly from epithelial cells in culture. GlpQ therefore allows choline to be transferred from the host to the bacterial cell surface.

Adult↗
PubMed2001

Inhibition of the rat blood-brain barrier choline transporter by manganese chloride.

Choline transport has been characterized by multiple mechanisms including the blood-brain barrier (BBB), and high- and low-affinity systems. Each mechanism has unique locations and characteristics yet retain some similarities. Previous studies have demonstrated cationic competition by monovalent cations at the BBB and cation divalent manganese in the high-affinity system. To evaluate the effects of divalent manganese inhibition as well as other cationic metals at the BBB choline transporter, brain choline uptake was evaluated in the presence of certain metals of interest in Fischer-344 rats using the in situ brain perfusion technique. Brain choline uptake was inhibited in the presence of Cd(2+) (73 +/- 2%) and Mn(2+) (44 +/- 6%), whereas no inhibition was observed with Cu(2+) and Al(3+). Furthermore, it was found that manganese caused a reduction in brain choline uptake and significant regional choline uptake inhibition in the frontal and parietal cortex, the hippocampus and the caudate putamen (45 +/- 3%, 68 +/- 18%, 58 +/- 9% and 46 +/- 15%, respectively). These results suggest that choline uptake into the CNS can be inhibited by divalent cationic metals and monovalent cations. In addition, the choline transporter may be a means by which manganese enters the brain.

Animals↗
PubMed2002

The neuronal choline transporter CHT1 is regulated by immunosuppressor-sensitive pathways.

The immunosuppressor cyclosporin A inhibits the peptidyl-prolyl-cis/trans-isomerase activity of cyclophilins and the resulting complex inhibits the phosphatase activity of calcineurin. Both enzymes were detected in peripheral nerve endings isolated from the electric organ of Torpedo and shown to be affected by 10 micro m cyclosporin A. Among the cholinergic properties studied, choline uptake was specifically inhibited by cyclosporin A to a maximum of 40%. Cyclosporin A decreased the rate of choline transport but not the binding of the non-transportable choline analogue hemicholinium-3, indicating that the number of membrane transporters was not affected. Through the use of two other immunosuppressors, FK506, which also inhibits calcineurin, and rapamycin, which does not, two different mechanisms of choline uptake inhibition were uncovered. FK506 inhibited the rate of choline transport, whereas rapamycin diminished the affinity for choline. The Torpedo homologue of the high affinity choline transporter CHT1 was cloned and its activity was reconstituted in Xenopus oocytes. Choline uptake by oocytes expressing tCHT1 was inhibited by all three immunosuppressors and also by microinjection of the specific calcineurin autoinhibitory domain A457-481, indicating that the phosphatase calcineurin regulates CHT1 activity and could be the common target of cyclosporin and FK506. Rapamycin, which changed the affinity of the transporter, may have acted through an immunophilin on the isomerization of critical prolines that are found in the tCHT1 sequence.

Animals↗
PubMed1996

Choline acetyltransferase immunoreactivity in the human small and large intestine.

BACKGROUND & AIMS: Choline acetyltransferase, an enzyme involved in the synthesis of acetylcholine, is a marker of cholinergic neurons. In this study, the distribution of choline acetyltransferase immunoreactivity in human intestine is described. METHODS: Frozen-section and whole-mount preparations of human small and large bowels were made and labeled with antiserum to choline acetyltransferase. Double labeling with antiserum to neuron-specific enolase enabled the proportion of all neurons that were immunoreactive for choline acetyltransferase to be determined. RESULTS: Nerve fibers, immunoreactive for choline acetyltransferase, were frequent in the circular and longitudinal muscle layers and were widespread in the myenteric and submucous plexuses, but none was observed in the mucosa. Myenteric neurons, immunoreactive for choline acetyltransferase, showed various morphologies, the most common being unipolar and having an irregular outline with several short, lamellar processes. Sixty-four percent of all myenteric neurons were immunoreactive for choline acetyltransferase. Cholinergic submucous neurons were homogeneous in appearance with oval, smooth cell bodies and filamentous dendrites and accounted for 53% of all submucous neurons. A number of cells resembling enteroendocrine cells in the epithelium of the small and large bowels had intense choline acetyltransferase immunoreactivity. CONCLUSIONS: The majority of neurons in human small and large intestines are cholinergic.

Aged↗
PubMed1987

Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line.

Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used as precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here we used a population of purely cholinergic cells (human neuroblastoma, LA-N-2), incubated in the presence of [methyl-3H]methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. PtdCho, purified by thin-layer chromatography, contained 90% of the label incorporated into lipids, demonstrating that LA-N-2 cells contained phosphatidylethanolamine N-methyltransferase. Three peaks of radioactive material that cochromatographed with authentic Ac-Cho, choline, and phosphocholine were observed when the water-soluble metabolites of the [3H]PtdCho were purified by high-performance liquid chromatography. Their identities were ascertained by subjecting them to enzymatic modifications with acetylcholinesterase, choline oxidase, and alkaline phosphatase, respectively. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine.

Acetylcholine↗
PubMed2000

Turnover of phosphatidylcholine in Saccharomyces cerevisiae. The role of the CDP-choline pathway.

The regulation of phosphatidylcholine degradation as a function of the route of phosphatidylcholine (PC) synthesis and changing environmental conditions has been investigated in the yeast Saccharomyces cerevisiae. In the wild-type strains studied, deacylation of phosphatidylcholine to glycerophosphocholine is induced when choline is supplied to the culture medium and, also, when the culture temperature is raised from 30 to 37 degrees C. In strains bearing mutations in any of the genes encoding enzymes of the CDP-choline pathway for phosphatidylcholine biosynthesis (CKI1, choline kinase; CPT1, 1, 2-diacylglycerol choline phosphotransferase; PCT1, CTP:phosphocholine cytidylyltransferase), no induction of phosphatidylcholine turnover and glycerophosphocholine production is seen in response to choline availability or elevated temperature. In contrast, the induction of phosphatidylcholine deacylation does occur in a strain bearing mutations in genes encoding enzymes of the methylation pathway for phosphatidylcholine biosynthesis (i.e. CHO2/PEM1 and OPI3/PEM2). Whereas the synthesis of PC via CDP-choline is accelerated when shifted from 30 to 37 degrees C, synthesis of PC via the methylation pathway is largely unaffected by the temperature shift. These results suggest that the deacylation of PC to GroPC requires an active CDP-choline pathway for PC biosynthesis but not an active methylation pathway. Furthermore, the data indicate that the synthesis and turnover of CDP-choline-derived PC, but not methylation pathway-derived PC, are accelerated by the stress of elevated temperature.

Cytidine Diphosphate Choline↗
PubMed2004

Nutritional importance of choline for brain development.

Choline is a dietary component essential for normal function of all cells. In 1998 the National Academy of Sciences, USA, issued a report identifying choline as a required nutrient for humans and recommended daily intake amounts. In ongoing studies we are finding that men have a higher requirement than do postmenopausal women, who in turn need more than premenopausal women. Pregnancy and lactation are periods when maternal reserves of choline are depleted. At the same time, the availability of choline for normal development of brain is critical. When rat pups received choline supplements (in utero or during the second week of life), their brain function is changed, resulting in lifelong memory enhancement. This change in memory function appears to be due to changes in the development of the memory center (hippocampus) in brain. These changes are so important that investigators can pick out the groups of animals whose mothers had extra choline even when these animals are elderly. Thus, memory function in the aged is, in part, determined by what mother ate. Foods highest in total choline concentrations per 100 g were beef liver (418 mg), chicken liver (290 mg), and eggs (251 mg). We suggest that choline-rich foods are an important component of the diet and that especially during pregnancy it would be prudent to include them as part of a healthy diet.

Animals↗
PubMed2006

Investigations on the effects of rape oil quality, choline and methionine concentration in diets for laying hens on the trimethylamine content of the eggs, on trimethylamine metabolism and on laying performance.

An experiment was conducted to study the effects of graded levels of choline addition (0, 500, 1000 and 4000 mg/kg diet) in laying hen diets prepared either with degummed or refined rape oil on the performance, sensory properties and trimethylamine (TMA) contents of the eggs. Furthermore, the diets containing no supplemented choline or 4000mg choline/kg diet were tested with adequate or inadequate methionine supply (4.2 vs. 2.8 g methionine/kg diet). TMA metabolism and N-balance were measured for the latter diet types, but only with the diets containing refined rape oil. Therefore, a total of 12 and 4 diets were tested in the feeding (n = 60) and balance study (n = 9). Laying performance (23 -75 weeks of age) was not significantly influenced by increasing choline additions with the exception of feed-to-egg mass ratio which decreased significantly linearly (P(linear) = 0.003). However, a significant interaction between choline addition and laying month was detected which was caused by a depression of performance of the unsupplemented control group occurring from the sixth laying month. The most obvious effect of an inadequate methionine supply was a temporary drop in performance between the third and sixth laying months. The mean TMA-concentration in pooled egg yolks [microg/g] increased with dietary choline concentration [mg/kg] in an exponentially related fashion (y = 1.14 + 4E(-10) x x(2.71), r2 = 0.962) and suggested only a minor influence of total dietary choline on TMA content up to approximately 2000mg choline/kg. Individual TMA-concentrations varied greatly from 0.4 - 1.5 microg/g, from 2.2 - 34 microg/g and from 18.4 - 75 microg/g for eggs with a normal, aberrant and heavily aberrant odour, respectively. It is concluded that a total choline concentration of at least approximately 1500 mg/kg is necessary to maintain a maximal laying performance. An inadequate methionine supply cannot be compensated by an increased addition of choline. Neither degummed nor refined rape oil influenced the TMA content of eggs.

Analysis of Variance↗
PubMed1988

Effect of dietary choline on volatile fatty acids in rumen liquid of sheep and rumen dry matter degradability of untreated and ammonia-treated wheat straw.

Three rumen fistulated wethers consumed a roughage (1200 g artificially dried grass) or a concentrate/roughage diet (600 g concentrate, 400 g dried grass per animal and day). The diets were unsupplemented or 0.5, 1 or 2 g choline per animal and day were added. After a 14-day feeding period, samples of rumen liquid were taken 0, 1, 2, 3, 4 and 6 h after morning feeding. In a second experiment, untreated and ammonia-treated wheat straw were incubated in nylon bags for 6, 12, 24, 48 and 72 h in rumen of 5 sheep fed on 1.2 kg dried grass and without or with 1 g choline per day. Choline supplementation decreased the total concentration of volatile fatty acids in rumen liquid in both types of diet (roughage: 106, 83, 89 and 87; concentrate/roughage: 142, 114, 91 and 106 mmol/l for 0, 0.5, 1 and 2 g choline per day resp.). Concentration of acetate and branched chain fatty acids in both diets and butyrate in concentrate/roughage diet was reduced as total acids. Butyrate in roughage diet was increased by added choline. Molar propionate concentration was not significantly influenced by choline (P greater than 0.05). Choline resulted in a little increase (P greater than 0.05) of dry matter degradability in rumen, especially when NH3-treated straw was incubated. The effect of choline on milk fat production of cows fed with diets rich in concentrate is probably not related to changes in rumen fermentation and digestion.

Acetates↗
PubMed1999

The effect of a combined dietary treatment with cholesterol and cholic acid on the lipid metabolism of geese at low or high choline concentrations.

A previous study demonstrated that a dietary treatment of young geese with cholesterol and cholic acid raises lipid concentrations in the liver. The present study was carried out to investigate whether such a lipid accumulation caused by those hyperlipidemic compounds can be intensified by low dietary choline concentrations. Therefore, 38 eight-week old geese were divided into four groups of 9 or 10 animals each and received a basal diet poor in choline which consisted predominately of maize and soy protein isolate over a period of 8 weeks. Treatment factors were supplementation of diets with cholesterol and cholic acid (0 vs. 5 g of cholesterol and cholic acid each per kg) and supplementation of choline chloride (0 vs. 1.5 g/kg). Final body weights as well as carcass weights were neither influenced significantly by dietary treatment with cholesterol and cholic acid nor by low dietary choline concentrations. However, feeding diets supplemented with cholesterol and cholic acid markedly increased liver weights (two-fold), hepatic triglyceride (3.7-fold) and cholesterol (12-fold) concentrations and percentages of monounsaturated fatty acids at the expense of saturated and polyunsaturated fatty acids in the liver. In geese fed diets with cholesterol and cholic acid, insufficient choline supply did not intensify, but even slightly reduced hepatic lipid accumulation. Geese fed diets with cholesterol and cholic acid exhibited markedly increased levels of cholesterol, triglycerides and phospholipids in plasma and very low-density lipoproteins, regardless of the choline supply. Muscle tissue of geese fed diets supplemented with cholesterol and cholic acid exhibited also increased concentrations of triglycerides and cholesterol whereas the fatty acid composition of muscle lipids remained unchanged. Among geese without hyperlipidemic treatment, concentrations of triglycerides in plasma and very low-density lipoproteins as well as the concentrations of phosphatidylcholine in liver and muscle tissue were not reduced by low dietary choline concentrations. Therefore, it is suggested that those animals were able to synthesize endogenous sufficient choline.

Animals↗
PubMed1997

Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release.

The exogenous administration of cytidine-5'-diphosphate (CDP)-choline has been used extensively as a brain activator in different neurological disorders that are associated with memory deficits. A total of 50 rats were utilized to (a) determine whether exogenously administered CDP-choline could attenuate posttraumatic motor and spatial memory performance deficits and (b) determine whether intraperitoneal (i.p.) administration of CDP-choline increases acetylcholine (ACh) release in the dorsal hippocampus and neocortex. In the behavioral study, traumatic brain injury (TBI) was produced by lateral controlled cortical impact (2-mm deformation/6 m/sec) and administered CDP-choline (100 mg/kg) or saline daily for 18 days beginning 1 day postinjury. At 1 day postinjury, rats treated with CDP-choline 15 min prior to assessment performed significantly better than saline-treated rats. Between 14-18 days postinjury, CDP-choline-treated rats had significantly less cognitive (Morris water maze performance) deficits that injured saline-treated rats. CDP-choline treatment also attenuated the TBI-induced increased sensitivity to the memory-disrupting effects of scopolamine, a muscarinic antagonist. The microdialysis studies demonstrated for the first time that a single i.p. administration of CDP-choline can significantly increase extracellular levels of ACh in dorsal hippocampus and neocortex in normal, awake, freely moving rats. This article provides additional evidence that spatial memory performance deficits are, at least partially, associated with deficits in central cholinergic neurotransmission and that treatments that enhance ACh release in the chronic phase after TBI may attenuate cholinergic-dependent neurobehavioral deficits.

Acetylcholine↗
PubMed1986

Plasma choline concentration in humans fed parenterally.

Choline is an essential nutrient for some mammals; it is used for membrane and neurotransmitter synthesis. We analyzed plasma samples, obtained periodically during TPN therapy, for choline concentration. Malnourished patients referred to a nutrition support service were prospectively assigned to be treated with daily infusions of amino acids with, and without, supplemental daily infusions of lipid emulsion for a period of 1 wk. After the first week, all subjects received intravenous lipid, and most were offered enteral food supplements. Initial plasma choline concentrations in the 25 malnourished patients were significantly lower than those measured in plasma samples from 23 hospitalized patients known to be eating well (6.5 +/- 0.6 vs 9.7 +/- 0.7 nmol/ml; mean +/- SEM; p less than 0.001). During the first week of TPN therapy, plasma choline concentrations in the lipid-restricted group tended to decrease (from 7.3 +/- 1.0 to 4.7 +/- 0.5 nmol/ml; mean +/- SEM; p less than 0.05), while in the lipid-supplemented group plasma choline tended to increase (from 5.6 +/- 0.5 to 6.2 +/- 0.7 nmol/ml; mean +/- SEM; p less than 0.05). Plasma choline concentration increased during wk 2-4, when all patients were treated with lipid emulsions, and some were offered enteral foods. We conclude that malnourished humans who eat no choline have diminished stores of plasma (and possibly tissue) choline.

Adult↗
PubMed1997

Prolonged fasting in humans results in diminished plasma choline concentrations but does not cause liver dysfunction.

Choline is a major donor of methyl groups, a precursor for membrane synthesis, and a component of the neurotransmitter acetylcholine. Choline-deficient diets deplete humans of choline and cause hepatic dysfunction and steatosis. In this study we determined whether acute starvation also depletes choline, as indicated by changes in plasma choline or phosphatidylcholine. Healthy humans (n = 10) fasted for 7 d, ingesting only water and mineral-vitamin supplements. Their mean (+/- SEM) plasma choline concentration was 9.5 +/- 0.5 micromol/L at the start of the study and dropped to 7.8 +/- 0.3 micromol/L after 1 wk of fasting (P < 0.01). The plasma phosphatidylcholine concentration did not change significantly (2.2 +/- 0.1 mmol/L at the start of the study and 2.4 +/- 0.2 mmol/L after 1 wk of fasting). Capacity of the liver to secrete lipoproteins was not affected by prolonged fasting. The mean plasma concentration of low-density-lipoprotein cholesterol was 3.3 +/- 0.2 mmol/L (126 +/- 8 mg/dL) at the start of the study and 4.9 +/- 0.5 mmol/L (188 +/- 19 mg/dL) after 1 wk of fasting. Liver damage assessed by serum alanine aminotransferase activity occurred in only 1 of 10 subjects. We conclude that prolonged fasting in humans modestly diminished plasma choline but was not associated with signs of choline deficiency, such as perturbed lipoprotein secretion and liver damage.

Adult↗
PubMed1992

Choline enhances acetylaminofluorene promotion of liver carcinogenesis in female but not in male rats.

The growth of focal lesions during chemical carcinogenesis has been analyzed after promotion in the liver of female and male rats receiving choline for 4 or 5 weeks. The number and size of foci of altered hepatocytes were first evaluated after methylnitrosourea was used as initiator and 2-acetylaminofluorene (2-AAF) associated with carbon tetrachloride as promoter. The development of enzyme-altered foci was lower in female rats than in males. Choline given intragastrically stimulated the growth of focal lesions in female rats by increasing both the enzyme-positive area of the single focus and the total area of positive foci per cm2 of liver section up to levels close to those of males. No effect of choline was observed in males. In a second set of experiments, focal proliferative lesions induced with the Solt-Farber model were larger in females fed a choline-enriched diet during the promotion phase, as a result of the area of the focus and the total area of foci per cm2 of liver being higher than that in females not receiving choline, with no significant change in the number of foci. When cell proliferation was selected during promotion by 2-AAF and carbon tetrachloride instead of partial hepatectomy, the effect of the choline-enriched diet was even more pronounced. This difference might be accounted for by the greater hepatotoxicity of xenobiotics after choline administration. The hypothesis that choline may enhanced hepatocyte susceptibility towards 2-AAF action by an increase in drug toxicity is discussed.

2-Acetylaminofluorene↗
PubMed2003

Carnitine and choline supplementation with exercise alter carnitine profiles, biochemical markers of fat metabolism and serum leptin concentration in healthy women.

We sought to determine the effects of supplementary choline, carnitine and a combination of the two with or without exercise on serum and urinary carnitine and biochemical markers of fatty acid oxidation in healthy humans. Nineteen women were placed in three groups: 1) placebo, choline or carnitine preloading period of 1 wk followed by 2) supplementation with choline plus carnitine during wk 2-wk 3 and 3) all groups exercised in wk 3. Although there were no changes in the placebo group, serum and urinary carnitine decreased in the choline-supplemented group during wk 1. Introduction of carnitine to the choline group restored serum and urinary carnitine. Serum and urinary carnitine increased during wk 1 in the carnitine-supplemented group and, although the introduction of choline to this group depressed serum and urinary carnitine, they remained significantly greater than control. Serum beta-hydroxybutyrate and serum as well as urinary acetylcarnitine were elevated by the supplements. A mild exercise regimen increased the concentration of serum beta-hydroxybutyrate, and serum and urinary acylcarnitines; it also decreased serum leptin concentrations in all groups. The effects of supplements were sustained until wk 2 after cessation of choline plus carnitine supplementation and exercise. We conclude that the choline-induced decrease in serum and urinary carnitine is buffered by carnitine preloading, and these supplements shift tissue partitioning of carnitine that favors fat mobilization, incomplete oxidation of fatty acids and disposal of their carbons in urine as acylcarnitines in humans.

3-Hydroxybutyric Acid↗