RESUMEN
Early life nutrition critically impacts post-natal brain maturation and cognitive development. Post-natal dietary deficits in specific nutrients, such as lipids, minerals or vitamins are associated with brain maturation and cognitive impairments. Specifically, polar lipids (PL), such as sphingolipids and phospholipids, are important cellular membrane building blocks and are critical for brain connectivity due to their role in neurite outgrowth, synaptic formation, and myelination. In this preclinical study, we assessed the effects of a chronic supplementation with a source of PL extracted from an alpha-lactalbumin enriched whey protein containing 10% lipids from early life (post-natal day (PND) 7) to adulthood (PND 72) on adult motor skills, anxiety, and long-term memory. The motor skills were assessed using open field and rotarod test. Anxiety was assessed using elevated plus maze (EPM). Long-term object and spatial memory were assessed using novel object recognition (NOR) and Morris water maze (MWM). Our results suggest that chronic PL supplementation improved measures of spatial long-term memory accuracy and cognitive flexibility in the MWM in adulthood, with no change in general mobility, anxiety and exploratory behavior. Our results indicate memory specific functional benefits of long-term dietary PL during post-natal brain development.
RESUMEN
Phospholipids (PL) or partial acylglycerols such as sn-1(3)-monoacylglycerol (MAG) are potent dietary carriers of long-chain polyunsaturated fatty acids (LC-PUFA) and have been reported to provide superior bioavailability when compared to conventional triacylglycerol (TAG). The main objective of the present study was to compare the incorporation of docosahexaenoic acid (DHA) in plasma, erythrocytes, retina and brain tissues in adult rats when provided as PL (PL-DHA) and MAG (MAG-DHA). Conventional dietary DHA oil containing TAG (TAG-DHA) as well as control chow diet were used to evaluate the potency of the two alternative DHA carriers over a 60-day feeding period. Fatty acid profiles were determined in erythrocytes and plasma lipids at time 0, 7, 14, 28, 35 and 49 days of the experimental period and in retina, cortex, hypothalamus, and hippocampus at 60 days. The assessment of the longitudinal evolution of DHA in erythrocyte and plasma lipids suggest that PL-DHA and MAG-DHA are efficient carriers of dietary DHA when compared to conventional DHA oil (TAG-DHA). Under these experimental conditions, both PL-DHA and MAG-DHA led to higher incorporations of DHA erythrocytes lipids compared to TAG-DHA group. After 60 days of supplementation, statistically significant increase in DHA level incorporated in neural tissues analyzed were observed in the DHA groups compared with the control. The mechanism explaining hypothetically the difference observed in circulatory lipids is discussed.
Asunto(s)
Ácidos Grasos/farmacocinética , Monoglicéridos/sangre , Fosfolípidos/sangre , Triglicéridos/sangre , Animales , Disponibilidad Biológica , Composición Corporal , Dieta , Grasas de la Dieta/administración & dosificación , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Eritrocitos/metabolismo , Ácidos Grasos/administración & dosificación , Ácidos Grasos/sangre , Masculino , Monoglicéridos/administración & dosificación , Fosfolípidos/administración & dosificación , Ratas , Ratas Wistar , Tamaño de la Muestra , Aceite de Soja/administración & dosificación , Aceite de Girasol/administración & dosificación , Triglicéridos/administración & dosificación , Aumento de PesoRESUMEN
Several acquired or congenital hypothalamic abnormalities may cause growth failure (GF). We described two of these congenital abnormalities. First, a case of CHARGE syndrome, an epigenetic disorder mostly caused by heterozygous mutations in the gene encoding CHD7, a chromatin remodeling protein, causing several malformations, some life-threatening, with additional secondary hypothalamus-hypophyseal dysfunction, including GF. Second, a cohort of individuals with genetic isolated severe GH deficiency (IGHD), due to a homozygous mutation in the GH-releasing hormone (GHRH) receptor gene described in Itabaianinha County, in northeast Brazil. In this IGHD, with marked reduction of serum concentrations of IGF-I, and an up regulation of IGF-II, GF is the principal finding in otherwise normal subjects, with normal quality of life and longevity. This IGHD may unveil the effects of GHRH, pituitary GH and IGF-I, IGF-II and local GH and growth factor on the size and function of body and several systems. For instance, anterior pituitary hypoplasia, and impairment of the non-REM sleep may be due to GHRH resistance. Proportionate short stature, doll facies, high-pitched pre-pubertal voice, and reduced muscle mass reflect the lack of the synergistic effect of pituitary GH and IGF-I in bones and muscles. Central adiposity may be due to a direct effect of the lack of GH. Brain, eyes and immune system may also involve IGF-II and local GH or growth factors. A concept of physiological hierarchy controlling body size and function by each component of the GH system may be drawn from this model.
Asunto(s)
Síndrome CHARGE/etiología , Enanismo Hipofisario/etiología , Trastornos del Crecimiento/etiología , Hipotálamo/anomalías , Mutación , Receptores de Neuropéptido/deficiencia , Receptores de Hormona Reguladora de Hormona Hipofisaria/deficiencia , Adulto , Preescolar , Femenino , Humanos , Masculino , Receptores de Neuropéptido/genética , Receptores de Hormona Reguladora de Hormona Hipofisaria/genéticaRESUMEN
Inflammatory bowel diseases are acute and chronic disabling inflammatory disorders with multiple complex etiologies that are not well-defined. Chronic intestinal inflammation has been linked to an energy-deficient state of gut epithelium with alterations in oxidative metabolism. Plasma-, urine-, stool-, and liver-specific metabonomic analyses are reported in a naïve T cell adoptive transfer (AT) experimental model of colitis, which evaluated the impact of long-chain n-3 polyunsaturated fatty acid (PUFA)-enriched diet. Metabolic profiles of AT animals and their controls under chow diet or fish oil supplementation were compared to describe the (i) consequences of inflammatory processes and (ii) the differential impact of n-3 fatty acids. Inflammation was associated with higher glycoprotein levels (related to acute-phase response) and remodeling of PUFAs. Low triglyceride levels and enhanced PUFA levels in the liver suggest activation of lipolytic pathways that could lead to the observed increase of phospholipids in the liver (including plasmalogens and sphingomyelins). In parallel, the increase in stool excretion of most amino acids may indicate a protein-losing enteropathy. Fecal content of glutamine was lower in AT mice, a feature exacerbated under fish oil intervention that may reflect a functional relationship between intestinal inflammatory status and glutamine metabolism. The decrease in Krebs cycle intermediates in urine (succinate, α-ketoglutarate) also suggests a reduction in the glutaminolytic pathway at a systemic level. Our data indicate that inflammatory status is related to this overall loss of energy homeostasis.
Asunto(s)
Traslado Adoptivo/métodos , Colitis/metabolismo , Colitis/prevención & control , Aceites de Pescado/farmacología , Metaboloma/fisiología , Metabolómica/métodos , Animales , Suplementos Dietéticos , Heces/química , Glutamina/análisis , Ácidos Cetoglutáricos/análisis , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Metaboloma/efectos de los fármacos , Ratones , Ácido Succínico/análisis , Orina/químicaRESUMEN
OBJECTIVE: To evaluate parathyroid function and mineral metabolism in psychiatric patients users of lithium salts. MATERIALS AND METHODS: We measured the serum levels of calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, albumin, parathyroid hormone (PTH), urea, creatinine, 25-hydroxy-vitamin D and lithium of 35 patients diagnosed with bipolar disorder in use of lithium carbonate (LC) for at least one year (Lithium Group - LG) and 35 healthy subjects (Control Group - CG). RESULTS: The LG and CG were matched by sex and age. There was only statistic difference in relation to the levels of PTH and ionized calcium, with p < 0.004 and p < 0.03, respectively. Secondary form of hyperparathyroidism (HPT) was found in eight (22.8%) LG patients and in none of the CG. There was no correlation between lithemia, usage time and dosage of LC. CONCLUSION: Our data demonstrate that lithium may create an imbalance in the parathyroid axis, characterized by elevated levels of PTH.
Asunto(s)
Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/metabolismo , Compuestos de Litio/uso terapéutico , Minerales/metabolismo , Glándulas Paratiroides/efectos de los fármacos , Adulto , Anciano , Fosfatasa Alcalina/sangre , Calcio/sangre , Estudios de Casos y Controles , Creatinina/sangre , Estudios Transversales , Femenino , Humanos , Hiperparatiroidismo Secundario/diagnóstico , Compuestos de Litio/sangre , Masculino , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/metabolismo , Persona de Mediana Edad , Glándulas Paratiroides/fisiología , Hormona Paratiroidea/sangre , Fósforo/sangre , Albúmina Sérica/análisis , Urea/sangre , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
Objective: To evaluate parathyroid function and mineral metabolism in psychiatric patients users of lithium salts. Materials and methods: We measured the serum levels of calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, albumin, parathyroid hormone (PTH), urea, creatinine, 25-hydroxy-vitamin D and lithium of 35 patients diagnosed with bipolar disorder in use of lithium carbonate (LC) for at least one year (Lithium Group – LG) and 35 healthy subjects (Control Group – CG). Results: The LG and CG were matched by sex and age. There was only statistic difference in relation to the levels of PTH and ionized calcium, with p < 0.004 and p < 0.03, respectively. Secondary form of hyperparathyroidism (HPT) was found in eight (22.8%) LG patients and in none of the CG. There was no correlation between lithemia, usage time and dosage of LC. Conclusion: Our data demonstrate that lithium may create an imbalance in the parathyroid axis, characterized by elevated levels of PTH. .
Objetivo: Avaliar a função paratireoidiana e o metabolismo mineral em pacientes psiquiátricos usuários de sais de lítio. Materiais e métodos: Foram avaliados os níveis séricos de cálcio total, cálcio iônico, fósforo inorgânico, fosfatase alcalina, albumina, paratormônio (PTH), ureia, creatinina, 25-hidroxivitamina D e lítio de 35 pacientes diagnosticados com transtorno afetivo bipolar usuários de carbonato de lítio (CL) há pelo menos um ano (Grupo Lítio – GL) e 35 indivíduos saudáveis (Grupo Controle – GC). Resultados: O GL e o GC foram pareados por sexo e idade. Somente se observou diferença estatística em relação aos níveis de PTH e cálcio iônico, com p < 0,004 e p < 0,03, respectivamente. Hiperparatireoidismo secundário foi encontrado em oito (22.8%) pacientes do GL e em nenhum do GC. No GL, não houve correlação entre litemia, tempo de uso e posologia do CL. Conclusão: Nossos dados demonstram que o lítio pode suscitar um desequilíbrio no eixo paratireoideano, caracterizado por níveis elevados de PTH. .
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/metabolismo , Compuestos de Litio/uso terapéutico , Minerales/metabolismo , Glándulas Paratiroides/efectos de los fármacos , Fosfatasa Alcalina/sangre , Estudios de Casos y Controles , Estudios Transversales , Calcio/sangre , Creatinina/sangre , Hiperparatiroidismo Secundario/diagnóstico , Compuestos de Litio/sangre , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/metabolismo , Glándulas Paratiroides/fisiología , Hormona Paratiroidea/sangre , Fósforo/sangre , Albúmina Sérica/análisis , Urea/sangre , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
BACKGROUND: Inflammatory bowel diseases (IBD) are chronic intestinal inflammatory diseases affecting about 1% of western populations. New eating behaviors might contribute to the global emergence of IBD. Although the immunoregulatory effects of omega-3 fatty acids have been well characterized in vitro, their role in IBD is controversial. METHODS: The aim of this study was to assess the impact of increased fish oil intake on colonic gene expression, eicosanoid metabolism and development of colitis in a mouse model of IBD. Rag-2 deficient mice were fed fish oil (FO) enriched in omega-3 fatty acids i.e. EPA and DHA or control diet for 4 weeks before colitis induction by adoptive transfer of naïve T cells and maintained in the same diet for 4 additional weeks. Onset of colitis was monitored by colonoscopy and further confirmed by immunological examinations. Whole genome expression profiling was made and eicosanoids were measured by HPLC-MS/MS in colonic samples. RESULTS: A significant reduction of colonic proinflammatory eicosanoids in FO fed mice compared to control was observed. However, neither alteration of colonic gene expression signature nor reduction in IBD scores was observed under FO diet. CONCLUSION: Thus, increased intake of dietary FO did not prevent experimental colitis.
Asunto(s)
Colitis/dietoterapia , Colitis/metabolismo , Eicosanoides/metabolismo , Aceites de Pescado/farmacología , Intestinos/efectos de los fármacos , Animales , Colitis/genética , Colon/fisiopatología , Citocinas/metabolismo , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Ácidos Grasos Omega-3/farmacología , Aceites de Pescado/química , Regulación de la Expresión Génica/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/etiología , Mucosa Intestinal/metabolismo , Ratones Endogámicos C57BL , Ratones Mutantes , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Colaboradores-Inductores/patologíaRESUMEN
The immunoregulatory effects of dietary omega-3 fatty acids are still not fully characterized. The aim of this study was to determine whether dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake limits intestinal ischemia-reperfusion (IR) injury. To test this, rats were fed either control or EPA/DHA supplemented diet for 3 weeks following which they underwent either a sham or an IR surgical protocol. A significant reduction in mucosal damage was observed after EPA/DHA supplemented diet as reflected by maintenance of total protein content. To address the underlying mechanisms of protection, we measured parameters of oxidative stress, intestinal and serological cytokines and intestinal eicosanoids. Interestingly, EPA/DHA fed animals displayed a higher activity of oxidative stress enzyme machinery, i.e., superoxide dismutase and catalase in addition to a reduction in total nitrate/nitrite content. While no changes in cytokines were observed, eicosanoid analyses of intestinal tissue revealed an increase in metabolites of the 12-lipoxygenase pathway following IR. Further, IR in EPA/DHA fed animals was accompanied by a significant increase of 17,18-epoxyeicosatetraenoic acid, 8-Iso prostaglandin F(3α) and thromboxane B(3), by more than 12-, 6-, 3-fold, respectively. Thus, the data indicate that EPA/DHA supplementation may be able to reduce early intestinal IR injury by anti-oxidative and anti-inflammatory mechanisms.
Asunto(s)
Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Intestinos/irrigación sanguínea , Intestinos/efectos de los fármacos , Daño por Reperfusión/prevención & control , Animales , Araquidonato 12-Lipooxigenasa/metabolismo , Ácidos Araquidónicos/metabolismo , Catalasa/metabolismo , Citocinas/metabolismo , Suplementos Dietéticos , Eicosanoides/metabolismo , Ácidos Grasos/análisis , Ácidos Grasos/química , Mucosa Intestinal/metabolismo , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Masculino , Arterias Mesentéricas/cirugía , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Superóxido Dismutasa/metabolismo , Tromboxanos/metabolismoRESUMEN
Orlistat is a gastric and pancreatic lipases inhibitor that is often prescribed to obese subjects. Orlistat has been shown to decrease the absorption of biologically important lipophilic micronutrients such as liposoluble vitamins. We hypothesized that long-term administration of orlistat may lower the incorporation of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in blood lipids and tissues. This hypothesis was tested in rats fed a diet supplemented with fish oil as a source of n-3 LC-PUFA. Male Wistar rats (n = 18) were divided into 3 groups and fed experimental high-fat diets containing fish oil (control diet) or fish oil plus orlistat (200 and 400 mg/kg of diet) over the course of 3 weeks. Fat absorption and the level of eicosapentaenoic acid (EPA) and docosahexaenoic acid, among other fatty acids, in red blood cells, plasma, liver, and spleen, were measured at the end of the experimental period. The results show that at 200 mg and 400 mg/kg of diet orlistat lowers fat absorption by 9% (P = .008) and 54% (P = .008). Orlistat given at the higher level induced a reduction of the incorporation of EPA in red blood cell (-45%; P = .006) and in plasma (-34%; P = .026) compared to the control group. Our results confirmed that administration of orlistat reduces incorporation of n-3 LC-PUFA in blood lipids and tissues in a rat model.
Asunto(s)
Grasas de la Dieta/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Inhibidores Enzimáticos/farmacología , Aceites de Pescado/metabolismo , Lactonas/farmacología , Lipasa/antagonistas & inhibidores , Animales , Sangre/metabolismo , Suplementos Dietéticos , Eritrocitos/metabolismo , Absorción Intestinal , Hígado/metabolismo , Masculino , Orlistat , Ratas , Ratas Wistar , Bazo/metabolismoRESUMEN
The flavonoids (-)-epigallocatechin-3-gallate (EGCg) and (-)-epicatechin-3-gallate (ECg) are major components of green tea and show numerous biological effects. We investigated the glucuronidation of these compounds and of quercetin by microsomes. Quercetin was almost fully glucuronidated by liver microsomes after 3 h, whereas ECg and ECGg were conjugated to a lesser extent (12.2 +/- 0.2 and 7.5 +/- 0.2%, respectively). The intestinal microsomes also glucuronidated quercetin much more efficiently than ECg and EGCg. Although the rates were lower than quercetin, intestinal microsomes exhibited higher activity on the galloyl group of ECg and EGCg compared to the flavonoid ring, whereas hepatic glucuronidation was higher on the flavonoid ring of EGCg and ECg compared to the galloyl groups. The low glucuronidation rates could partially explain why these flavanols are present in plasma as unconjugated forms.