RESUMEN
OBJECTIVES: Choline (Ch) is an essential nutrient that acts as a cognitive facilitator when administered during perinatal periods, and it has been recognised as a 'pharmacological' agent that can ease cognitive dysfunctions provoked by exposure to damaging stimuli during early developmental stages. The aim of the present work is to determine whether providing a diet rich in Ch would reduce the severity of the memory deficit provoked by a neonatal stress episode in male adult rats. METHODS: The effect of Ch on memory was measured using memory tasks such as object and place recognition. Ontogenetic manipulations were conducted during two sensitive developmental periods. During the first post-natal (PN) 14 days, only the male rat pups were selected and half of them were separated from the mother, group maternal separation (MS). Subsequently, during periadolescence (PN 21-60), the rats were exposed to a deficient (DEF = 0 g/kg Ch chloride), sufficient (CON = 1.1 g/kg Ch chloride), or supplemented (SUP = 5 g/kg Ch chloride) diets for this nutrient. RESULTS: The results indicated that for group MS, only rats fed with the SUP diet were able to recognise the familiar object and place that had been experienced 24 hours before, unlike groups DEF and CON. In addition, whereas rats in the non-separated group (No-MS) recognised the object independently of the diet, only rats that received a DEF diet failed to recognise the place, showing that a Ch deficit affects spatial memory tasks. DISCUSSION: These results show that Ch supplementation during periadolescence can attenuate the memory deficit provoked by extended neonatal stress.
Asunto(s)
Colina/uso terapéutico , Trastornos del Conocimiento/prevención & control , Suplementos Dietéticos , Privación Materna , Trastornos de la Memoria/prevención & control , Neurogénesis , Fármacos Neuroprotectores/uso terapéutico , Animales , Animales Recién Nacidos , Deficiencia de Colina/dietoterapia , Deficiencia de Colina/fisiopatología , Trastornos del Conocimiento/etiología , Masculino , Memoria , Trastornos de la Memoria/etiología , Distribución Aleatoria , Ratas Wistar , Reconocimiento en Psicología , Memoria EspacialRESUMEN
Evidence indicates that hepatic fibrosis is the initial lesion of cirrhosis or hepatocellular carcinoma in diseases such as nonalcoholic steatohepatitis (NASH). To induce NASH, we fed rats a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet. Histopathological examination revealed that fibrosis appeared from week 4 and progressed to bridging fibrosis from week 12. Using qRT-PCR assays, we detected increased expression of miR-21, Mmp-9, and Timp-1 in liver that peaked during week 4, when fibrosis was first detected. The expression pattern of miR-21 in plasma paralleled that in liver. Fibrosis tended to be resolved within 12 weeks of a recovery period after 12 weeks of feeding, and the expression of miR-21, Timp-1, and Mmp-9 decreased in liver. Comprehensive analyses of miRNA and mRNA expression in the liver using samples acquired at week 4 detected 16 miRNAs and 11 mRNAs that are mutually-interacting fibrosis-related factors. We therefore conclude that miR-21 was closely associated with fibrosis in a rat model of NASH and has potential as a plasma biomarker for hepatic fibrosis.
Asunto(s)
Modelos Animales de Enfermedad , Cirrosis Hepática/etiología , Hígado/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , MicroARNs/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Animales , Biomarcadores/sangre , Colina/uso terapéutico , Deficiencia de Colina/complicaciones , Deficiencia de Colina/dietoterapia , Deficiencia de Colina/etiología , Deficiencia de Colina/fisiopatología , Dieta/efectos adversos , Suplementos Dietéticos/envenenamiento , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/fisiopatología , Hierro de la Dieta/envenenamiento , Hígado/inmunología , Hígado/patología , Hígado/fisiopatología , Cirrosis Hepática/prevención & control , Metaloproteinasa 9 de la Matriz/genética , MicroARNs/sangre , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , ARN Mensajero/metabolismo , Ratas Wistar , Organismos Libres de Patógenos Específicos , Inhibidor Tisular de Metaloproteinasa-1/genéticaRESUMEN
OBJECTIVES: Adequate choline supply during the perinatal period is critical for proper brain formation, when robust neurogenesis and neuronal maturation occur. Therefore, the objective of this study was to examine the impact of perinatal choline status on neurodevelopment. METHODS: Sows were fed a choline-deficient (CD) or choline-sufficient (CS) diet during the last half of the gestational period. At 2 days of age, piglets from sows within each prenatal treatment group were further stratified into postnatal treatment groups and provided either a CD or CS milk replacer, resulting in four treatment groups. At 30 days of age, piglets underwent magnetic resonance imaging (MRI) procedures to analyze structural and metabolite differences. RESULTS: Single-voxel spectroscopy (SVS) analysis revealed postnatally CS piglets had higher (P < 0.001) concentrations of glycerophosphocholine-phosphocholine than postnatally CD piglets. Volumetric analysis indicated smaller (P < 0.006) total brain volumes in prenatally CD piglets compared with prenatally CS piglets. Differences (P < 0.05) in the corpus callosum, pons, midbrain, thalamus, and right hippocampus, were observed as larger region-specific volumes proportional to total brain size in prenatally CD piglets compared with CS piglets. Diffusion tensor imaging (DTI) suggested interactions (P < 0.05) between prenatal and postnatal choline status in fractional anisotropy values of the thalamus and right hippocampus. Prenatally CS piglets had lower cerebellar radial diffusivity (P = 0.045) compared with prenatally CD piglets. DISCUSSION: This study demonstrates that prenatal choline deficiency has profound effects by delaying neurodevelopment as evidenced by structural and metabolic MRI assessments.
Asunto(s)
Encéfalo/patología , Deficiencia de Colina/fisiopatología , Modelos Animales de Enfermedad , Desarrollo Fetal , Retardo del Crecimiento Fetal/etiología , Fenómenos Fisiologicos Nutricionales Maternos , Neurogénesis , Animales , Animales Recién Nacidos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Colina/metabolismo , Colina/uso terapéutico , Deficiencia de Colina/dietoterapia , Dieta/efectos adversos , Imagen de Difusión Tensora , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/patología , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Tamaño de los Órganos , Fosfatidilcolinas/metabolismo , Fosforilcolina/metabolismo , Embarazo , Sus scrofaRESUMEN
PURPOSE: The aim of this work was to investigate the potential protective effects of fish oil on the basis of kidney transcriptomic data on a nutritional experimental model. METHODS: Male weanling Wistar rats were divided into four groups and fed choline-deficient (CD) and choline-supplemented (CS) diets with vegetable oil (VO) and menhaden oil (MO): CSVO, CDVO, CSMO and CDMO. Animals were killed after receiving the diets for 6 days. Total RNA was purified from the right kidney and hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array. Differentially expressed genes were analyzed. RESULTS: All CSVO, CSMO and CDMO rats showed no renal alterations, while all CDVO rats showed renal cortical necrosis. A thorough analysis of the differential expression between groups CSMO and CDMO was carried out. There were no differential genes for p < 0.01. The analysis of the differential expression between groups CSVO and CSMO revealed 32 genes, 11 were over-expressed and 21 were under-expressed in CSMO rats. CONCLUSIONS: This work was part of a large set of experiments and was used in a hypothesis-generating manner. The comprehensive analysis of genetic expression allowed confirming that menhaden oil has a protective effect on this nutritional experimental model and identifying 32 genes that could be responsible for that protection, including Gstp1. These results reveal that gene changes could play a role in renal injury.
Asunto(s)
Lesión Renal Aguda/prevención & control , Deficiencia de Colina/dietoterapia , Suplementos Dietéticos , Aceites de Pescado/uso terapéutico , Riñón/metabolismo , Transcriptoma , Lesión Renal Aguda/etiología , Animales , Biomarcadores/sangre , Colina/uso terapéutico , Deficiencia de Colina/metabolismo , Deficiencia de Colina/patología , Deficiencia de Colina/fisiopatología , Perfilación de la Expresión Génica , Gutatión-S-Transferasa pi/genética , Gutatión-S-Transferasa pi/metabolismo , Riñón/patología , Riñón/fisiopatología , Masculino , Necrosis , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN/metabolismo , Ratas Wistar , Regulación hacia Arriba , DesteteRESUMEN
Choline is a B vitamin co-factor and its deficiency seems to impair heart function. Carnitine, a chemical analog of choline, has been used as adjunct in the management of cardiac diseases. The study investigates the effects of choline deficiency on myocardial performance in adult rats and the possible modifications after carnitine administration. Wistar Albino rats (n=24), about 3 months old, were randomized into four groups fed with: (a) standard diet (control-CA), (b) choline deficient diet (CDD), (c) standard diet and carnitine in drinking water 0.15% w/v (CARN) and (d) choline deficient diet and carnitine (CDD+CARN). After four weeks of treatment, we assessed cardiac function under isometric conditions using the Langendorff preparations [Left Ventricular Developed Pressure (LVDP-mmHg), positive and negative first derivative of LVDP were evaluated], measured serum homocysteine and brain natriuretic peptide (BNP) levels and performed histopathology analyses. In the CDD group a compromised myocardium contractility compared to control (P=0.01), as assessed by LVDP, was noted along with a significantly impaired diastolic left ventricular function, as assessed by (-) dp/dt (P=0.02) that were prevented by carnitine. Systolic force, assessed by (+) dp/dt, showed no statistical difference between groups. A significant increase in serum BNP concentration was found in the CDD group (P<0.004) which was attenuated by carnitine (P<0.05), whereas homocysteine presented contradictory results (higher in the CDD+CARN group). Heart histopathology revealed a lymphocytic infiltration of myocardium and valves in the CDD group that was reduced by carnitine. In conclusion, choline deficiency in adult rats impairs heart performance; carnitine acts against these changes.
Asunto(s)
Cardiotónicos/uso terapéutico , Carnitina/uso terapéutico , Deficiencia de Colina/dietoterapia , Suplementos Dietéticos , Ventrículos Cardíacos/fisiopatología , Disfunción Ventricular Izquierda/prevención & control , Animales , Cardiotónicos/efectos adversos , Carnitina/efectos adversos , Deficiencia de Colina/inmunología , Deficiencia de Colina/patología , Deficiencia de Colina/fisiopatología , Suplementos Dietéticos/efectos adversos , Edema Cardíaco/etiología , Edema Cardíaco/prevención & control , Fibrosis , Válvulas Cardíacas/inmunología , Válvulas Cardíacas/patología , Ventrículos Cardíacos/inmunología , Ventrículos Cardíacos/patología , Homocisteína/sangre , Hiperhomocisteinemia/etiología , Linfocitos/inmunología , Masculino , Contracción Miocárdica , Péptido Natriurético Encefálico/sangre , Distribución Aleatoria , Ratas , Ratas Wistar , Disfunción Ventricular Izquierda/etiologíaRESUMEN
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. Their infants (n = 99) were tested for short-term visuospatial memory, long-term episodic memory, language development, and global development at 10 and 12 mo of age. RESULTS: The women studied ate diets that delivered â¼360 mg choline/d in foods (â¼80% of the recommended intake for pregnant women, 65% of the recommended intake for lactating women). The phosphatidylcholine supplements were well tolerated. Groups did not differ significantly in global development, language development, short-term visuospatial memory, or long-term episodic memory. CONCLUSIONS: Phosphatidylcholine supplementation of pregnant women eating diets containing moderate amounts of choline did not enhance their infants' brain function. It is possible that a longer follow-up period would reveal late-emerging effects. Moreover, future studies should determine whether supplementing mothers eating diets much lower in choline content, such as those consumed in several low-income countries, would enhance infant brain development.
Asunto(s)
Desarrollo Infantil , Deficiencia de Colina/dietoterapia , Cognición , Suplementos Dietéticos , Lactancia , Fenómenos Fisiologicos Nutricionales Maternos , Fosfatidilcolinas/uso terapéutico , Deficiencia de Colina/etiología , Deficiencia de Colina/fisiopatología , Dieta/efectos adversos , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Recién Nacido , Desarrollo del Lenguaje , Masculino , Memoria a Largo Plazo , Memoria a Corto Plazo , North Carolina , Fosfatidilcolinas/efectos adversos , Embarazo , Complicaciones del Embarazo/dietoterapia , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
Choline is a ubiquitous water soluble nutrient, often associated with the B vitamins; however, not yet officially defined as a B vitamin. It is important in the synthesis of phospholipid components of cell membranes, and plasma lipoproteins, providing structural integrity as well as being important in cell signaling; it is also important in the synthesis of the neurotransmitter acetylcholine, and the oxidized form of choline, glycine betaine, serves as an important methyl donor in the methionine cycle. It is present in a wide variety of foods, and is endogenously synthesized in humans through the sequential methylation of phosphatidylethanolamine. The present article represents an introduction to the nutrition, metabolism, and physiological functions of choline and choline derivatives in humans. The association of choline and choline derivatives in risk of chronic disease, including: neural tube defects, coronary artery disease, cancer, Alzheimer's disease, dementia, and memory, and cystic fibrosis is reviewed.
Asunto(s)
Deficiencia de Colina/metabolismo , Colina/metabolismo , Estado Nutricional/fisiología , Animales , Colina/administración & dosificación , Colina/fisiología , Deficiencia de Colina/dietoterapia , Deficiencia de Colina/fisiopatología , Humanos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
Choline is an essential nutrient for humans. Metabolically choline is used for the synthesis of membrane phospholipids (e.g. phosphatidylcholine), as a precursor of the neurotransmitter acetylcholine, and, following oxidation to betaine, choline functions as a methyl group donor in a pathway that produces S-adenosylmethionine. As a methyl donor choline influences DNA and histone methylation--two central epigenomic processes that regulate gene expression. Because the fetus and neonate have high demands for choline, its dietary intake during pregnancy and lactation is particularly important for normal development of the offspring. Studies in rodents have shown that high choline intake during gestation improves cognitive function in adulthood and prevents memory decline associated with old age. These behavioral changes are accompanied by electrophysiological, neuroanatomical, and neurochemical changes and by altered patterns of expression of multiple cortical and hippocampal genes including those encoding key proteins that contribute to the biochemical mechanisms of learning and memory. These actions of choline are observed long after the exposure to the nutrient ended (months) and correlate with fetal hepatic and cerebral cortical choline-evoked changes in global- and gene-specific DNA cytosine methylation and with dramatic changes of the methylation pattern of lysine residues 4, 9 and 27 of histone H3. Moreover, gestational choline modulates the expression of DNA (Dnmt1, Dnmt3a) and histone (G9a/Ehmt2/Kmt1c, Suv39h1/Kmt1a) methyltransferases. In addition to the central role of DNA and histone methylation in brain development, these processes are highly dynamic in adult brain, modulate the expression of genes critical for synaptic plasticity, and are involved in mechanisms of learning and memory. A recent study documented that in a cohort of normal elderly people, verbal and visual memory function correlated positively with the amount of dietary choline consumption. It will be important to determine if these actions of choline on human cognition are mediated by epigenomic mechanisms or by its influence on acetylcholine or phospholipid synthesis.
Asunto(s)
Encéfalo/crecimiento & desarrollo , Colina/administración & dosificación , Colina/metabolismo , Metilación de ADN/fisiología , Histonas/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Deficiencia de Colina/dietoterapia , Deficiencia de Colina/metabolismo , Deficiencia de Colina/prevención & control , Femenino , Humanos , Estado Nutricional/fisiología , EmbarazoRESUMEN
Choline is an essential nutrient and can also be obtained by de novo synthesis via an oestrogen responsive pathway. Choline can be oxidised to the methyl donor betaine, with short-term supplementation reported to lower plasma total homocysteine (tHcy); however, the effects of longer-term choline supplementation are less clear. We investigated the effect of choline supplementation on plasma concentrations of free choline, betaine and tHcy and B-vitamin status in postmenopausal women, a group more susceptible to low choline status. We also assessed whether supplementation altered plasma lipid profiles. In this randomised, double-blinded, placebo-controlled study, forty-two healthy postmenopausal women received 1 g choline per d (as choline bitartrate), or an identical placebo supplement with their habitual diet. Fasting blood samples were collected at baseline, week 6 and week 12. Administration of choline increased median choline and betaine concentrations in plasma, with significant effects evident after 6 weeks of supplementation (P<0·001) and remaining significant at 12 weeks (P<0·001); no effect was observed on folate status or on plasma lipids. Choline supplementation induced a median (25th, 75th percentile) change in plasma tHcy concentration at week 6 of -0·9 (-1·6, 0·2) µmol, a change which, when compared to that observed in the placebo group 0·6 (-0·4, 1·9) µmol, approached statistical significance (P=0·058). Choline supplementation at a dose of 1 g/d significantly increases the circulating concentration of free choline, and can also significantly increase the concentration of the methyl donor, betaine, thereby potentially enhancing the betaine-homocysteine methyltransferase-mediated remethylation of tHcy.
Asunto(s)
Envejecimiento , Betaína/sangre , Deficiencia de Colina/dietoterapia , Colina/uso terapéutico , Suplementos Dietéticos , Estado Nutricional , Anciano , Biomarcadores/sangre , Colina/efectos adversos , Colina/sangre , Deficiencia de Colina/sangre , Deficiencia de Colina/fisiopatología , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Femenino , Ácido Fólico/sangre , Homocisteína/sangre , Humanos , Hiperhomocisteinemia/etiología , Hiperhomocisteinemia/prevención & control , Lípidos/sangre , Persona de Mediana Edad , Irlanda del Norte , Cooperación del Paciente , PosmenopausiaRESUMEN
BACKGROUND: Choline deficiency may develop in malnourished patients, those with cirrhosis, and those who require total parenteral nutrition. Previous data has suggested an important role for the kidneys in the maintenance of choline homeostasis. OBJECTIVE: This study was undertaken to determine the change in plasma choline during hemodialysis and to determine if it was lost in the dialysate. DESIGN: Thirteen adult patients (10 men, 3 women) who had required hemodialysis for a mean of 10.8 years were studied. Dialysis was performed 3 times weekly for 4 hours using either a cellulose acetate or polysulfone dialyzer membrane. Venous and arterial blood, and dialysate samples were taken for measurement of plasma free and phospholipid-bound choline concentration before beginning dialysis and after each hour of dialysis. An in vitro system was devised to determine if choline could bind to a significant degree to the dialysis membrane. RESULTS: Plasma free choline concentration was increased above normal (11.7 +/- 3.7 nmol/mL) at baseline and declined progressively during dialysis. In contrast, plasma phospholipid-bound choline concentration increased progressively during dialysis. The decrease in plasma free choline (-1.8 +/- 0.3 nmol/mL(-1)/h(-1); P = 1.6 x 10(-6)) was almost entirely related to that which was removed during dialysis, although the magnitude of the loss was not correlated with the increase in plasma phospholipid-bound choline concentration (125 +/- 20.5 nmol/mL(-1)/h(-1); P < 1.2 x 10(-6)). Patients lost a mean of 246 pmol of free choline during hemodialysis. Choline did not bind to the dialysis membrane. CONCLUSION: Plasma free choline concentration is elevated before dialysis, and choline is lost to a significant degree in the dialysate. Further investigation is necessary to determine whether a transient, dialysis-induced choline deficiency develops, and whether there is a role for choline supplementation in these patients. The choline homeostatic mechanism requires further investigation in renal failure patients.
Asunto(s)
Deficiencia de Colina/prevención & control , Colina/metabolismo , Soluciones para Hemodiálisis/química , Fallo Renal Crónico/complicaciones , Fosfolípidos/metabolismo , Diálisis Renal , Adulto , Colina/sangre , Deficiencia de Colina/dietoterapia , Femenino , Humanos , Técnicas In Vitro , Fallo Renal Crónico/terapia , Masculino , Nutrición Parenteral Total , Fosfolípidos/análisisRESUMEN
BACKGROUND: Epidemiological studies report an inverse relationship between intake of the B vitamin folic acid and colon cancer. Folate is important for DNA synthesis and repair. Moreover, the production of S-adenosylmethionine (SAM), essential for normal DNA methylation and gene expression, is dependent on folic acid. Folate deficiency may increase the risk of malignant transformation by perturbing these pathways. AIMS OF THE STUDY: The principal aim of this study was to determine the effects of folate deficiency on DNA stability and DNA methylation in rat colonocytes in vivo. As the metabolic pathways of folate and other dietary methyl donors are closely linked, the effects of methionine and choline deficiency were also evaluated. METHODS: Male Hooded-Lister rats were fed a diet deficient in folic acid, or in methionine and choline, or in folate, methionine and choline for 10 weeks. DNA strand breakage and misincorporated uracil were determined in isolated colonocytes using alkaline single cell gel electrophoresis. Global DNA methylation was measured in colonic scrapings. Folate was measured in plasma, erythrocyte and liver samples. RESULTS: Methyl donor deficiency induced DNA strand breakage in colonocytes isolated from all experimental groups. Uracil levels in colonocyte DNA remained unchanged compared with controls. DNA methylation was unaffected either by folate and/or methionine and choline depletion. Rats fed a folate-deficient diet had less folate in plasma, red blood cells and liver than controls. CONCLUSIONS: Folate and methyl deficiency in vivo primarily affects DNA stability in isolated colonocytes of rats, without affecting overall DNA methylation.