RESUMO
Obesity and insulin resistance are the key factors underlying the etiology of major health problems such as hypertension, diabetes and stroke. These important health issues lead researchers to investigate new approaches to prevent and treat obesity and insulin resistance. Good candidates are the phytochemical compounds that have been extensively studied in the field. Therefore, the aim of this study was to test whether sulforaphane (SFN, 1 mg kg⻹, 4 months treatment), a potent inducer of antioxidant enzymes present in cruciferous vegetables, had some beneficial effects on obesity and insulin resistance induced by a highly palatable (HP) diet in male Wistar rats. Glucose tolerance, serum and hepatic lipid levels, lipid profile, ALT, AST, urea and creatinine, GLUT1 and GLUT3 levels in the cerebral cortex, hippocampus and hypothalamus were analyzed. Glucose tolerance was lower in the HP diet groups, especially in the HP group treated with SFN. Except for the liver triacylglycerols, no differences were found in serum lipids, hepatic and kidney markers of the HP diet groups. Although expression of GLUT1 was similar between groups for all three brain structures analyzed, expression of GLUT3 in the cortex and hypothalamus had a tendency to decrease in the HP diet group treated with SFN. In conclusion, SFN at the specific dose was able to accentuate glucose intolerance and may affect GLUT3 expression in the cerebral cortex and hypothalamus.
Assuntos
Glicemia/metabolismo , Córtex Cerebral/metabolismo , Transportador de Glucose Tipo 3/metabolismo , Hipotálamo/metabolismo , Isotiocianatos/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Córtex Cerebral/efeitos dos fármacos , Transportador de Glucose Tipo 3/genética , Humanos , Hipotálamo/efeitos dos fármacos , Resistência à Insulina , Masculino , Obesidade/genética , Obesidade/metabolismo , Ratos , Ratos Wistar , SulfóxidosRESUMO
Consumption of energy-dense/high-fat diets is strongly and positively associated with overweight and obesity, which are associated with increase in the prevalence of certain chronic diseases. We evaluated the effect of hypercaloric/fat or normocaloric diets on some biochemical parameters in rats. Seventy-two rats were divided into four groups that were fed for 16 weeks with diets: normocaloric [9.12% soy oil, normocaloric soy oil (NSO)], hypercaloric olive oil [43.8% olive oil, hypercaloric olive oil (HOO)], hypercaloric saturated fat [43.8% saturated fat, hypercaloric saturated fat (HSF)] and normocaloric saturated fat [43.8% saturated fat, normocaloric saturated fat (NSF)]. HSF rats consumed more calories daily than the others and gained more retroperitoneal fat, although HSF and HOO rats had higher body weight. In liver, glycogen synthesis and concentration were higher in rats HSF and NSF. In plasma, total cholesterol (TC) levels were higher in HSF rats than in the others, and triacylglycerol (TAG) levels were lower in HOO and higher in HSF rats in relation to the others. In liver, TC and TAG were elevated in HSF, NSF and HOO rats. Paraoxonase 1 activity, which is related to high-density lipoprotein cholesterol and has anti-atherogenic role was lower in rats HSF. In HOO rats, glucose tolerance test was altered, but insulin tolerance test was normal. These results suggest that consumption of energy-dense/high-fat diets, both saturated or monounsaturated, causes damaging effects. However, more studies are necessary to understand the mechanisms by which these diets cause the metabolic alterations observed.
Assuntos
Glicemia/metabolismo , Dieta Hiperlipídica , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/administração & dosagem , Tecido Adiposo/metabolismo , Animais , Arildialquilfosfatase/sangue , Colesterol/sangue , Colesterol/metabolismo , Ingestão de Energia , Fezes/química , Teste de Tolerância a Glucose , Glicogênio/metabolismo , Homeostase , Fígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Azeite de Oliva , Óleos de Plantas/administração & dosagem , Ratos , Ratos Wistar , Óleo de Soja/administração & dosagem , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Aumento de PesoRESUMO
Obesity is frequently associated with consumption of high amounts of sugar and/or fat. Studies have demonstrated a high prevalence of overweight and obesity associated or not with increase rates of psychiatry disorders, in particular mood and anxiety disorders. Recent works have demonstrated an association between specific genes involved in oxidative stress metabolism and anxiety-like behavior. The aim of this study was to investigate the effect of a highly palatable diet enriched with sucrose in body fat mass composition, anxiety behavior and brain oxidative status. Twenty male Wistar rats received two different diets during four months: standard chow (SC) and highly palatable (HP). Metabolic parameters, behavioral tests and oxidative stress status were evaluated. Body fat mass, insulin sensitivity and glucose tolerance were altered in the HP group (p<0.01). The same group spends less time in light compartment and had a lower risk assessment behavior (p<0.05) but no differences were observed in the open field test habituation (p>0.05). Protein degradation, DCF and TBARS levels were not different in the hippocampus between groups; however, there were higher levels of protein degration in frontal cortex of HP groups (p<0.05), although DCF and TBARS levels don't differ from the SC group (p>0.05). In conclusion, our data suggest that the consumption of HP diet leads to an obese phenotype, increases protein oxidation in frontal cortex and appears to induce anxiety-like behavior in rats.
Assuntos
Ansiedade/psicologia , Comportamento Animal/fisiologia , Dieta , Proteínas do Tecido Nervoso/metabolismo , Córtex Pré-Frontal/metabolismo , Animais , Composição Corporal/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Radicais Livres/metabolismo , Teste de Tolerância a Glucose , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Proteínas do Tecido Nervoso/biossíntese , Estresse Oxidativo/fisiologia , Proteínas Tirosina Quinases/metabolismo , Ratos , Ratos Wistar , Sacarose/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triptofano/metabolismoRESUMO
Methylmalonic acid (MMA) is an endogenous convulsing compound that accumulates in methylmalonic acidemia, an inborn error of the metabolism characterized by severe neurological dysfunction, including seizures. The mechanisms by which MMA causes seizures involves the activation of the N-methyl-D-aspartate (NMDA) receptors, but whether GABAergic mechanisms are involved in the convulsions induced by MMA is not known. Therefore, in the current study we investigated the involvement of GABAergic mechanisms in the convulsions induced by MMA. Adult rats were injected (i.c.v.) with muscimol (46 pmol/1 microl), baclofen (0.03, 0.1 and 0.3 micromol/1 microl), MK-801 (6 nmol/1 microl), pyridoxine (2 micromol/4 microl) or physiological saline (0.15 micromol/1 microl). After 30 min, MMA (0.3, 0.1 and 3 micromol/1 microl) or NaCl (6 micromol/1 microl, i.c.v.) was injected. The animals were immediately transferred to an open field and observed for the appearance of convulsions. After behavioral evaluation, glutamic acid decarboxylase (GAD) activity was determined in cerebral cortex homogenates by measuring the 14CO2 released from l-[14C]-glutamic acid. Convulsions were confirmed by electroencephalographic recording in a subset of animals. MMA caused the appearance of clonic convulsions in a dose-dependent manner and decreased GAD activity in the cerebral cortex ex vivo. GAD activity negatively correlated with duration of MMA-induced convulsions (r=-0.873, P<0.01), in an individual basis. Muscimol, baclofen, MK-801 and pyridoxine prevented MMA-induced convulsions, but only MK-801 and pyridoxine prevented MMA-induced GAD inhibition. These data suggest GABAergic mechanisms are involved in the convulsive action of MMA, and that GAD inhibition by MMA depends on the activation of NMDA receptors. While in this study we present novel data about the role of the GABAergic system in MMA-induced convulsions, the central role of NMDA receptors in the neurochemical actions of MMA is further reinforced since they seem to trigger GABAergic failure.
Assuntos
Glutamato Descarboxilase/metabolismo , Ácido Metilmalônico , Convulsões/induzido quimicamente , Convulsões/enzimologia , Ácido gama-Aminobutírico/fisiologia , Análise de Variância , Animais , Baclofeno/farmacologia , Comportamento Animal/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Eletroencefalografia/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Agonistas GABAérgicos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Muscimol/farmacologia , Ratos , Ratos Wistar , Convulsões/fisiopatologiaRESUMO
Mitochondrial beta-ketothiolase and 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiencies are inherited neurometabolic disorders affecting isoleucine catabolism. Biochemically, beta-ketothiolase deficiency is characterized by intermittent ketoacidosis and urinary excretion of 2-methyl-acetoacetate (MAA), 2-methyl-3-hydroxybutyrate (MHB) and tiglylglycine (TG), whereas in MHBD deficiency only MHB and tiglylglycine accumulate. Lactic acid accumulation and excretion are also observed in these patients, being more pronounced in MHBD-deficient individuals, particularly during acute episodes of decompensation. Patients affected by MHBD deficiency usually manifest severe mental retardation and convulsions, whereas beta-ketothiolase-deficient patients present encephalopathic crises characterized by metabolic acidosis, vomiting and coma. Considering that the pathophysiological mechanisms responsible for the neurological alterations of these disorders are unknown and that lactic acidosis suggests an impairment of energy production, the objective of the present work was to investigate the in vitro effect of MAA and MHB, at concentrations varying from 0.01 to 1.0 mmol/L, on several parameters of energy metabolism in cerebral cortex from young rats. We observed that MAA markedly inhibited CO2 production from glucose, acetate and citrate at concentrations as low as 0.01 mmol/L. In addition, the activities of the respiratory chain complex II and succinate dehydrogenase were mildly inhibited by MAA. MHB, at 0.01 mmol/L and higher concentrations, strongly inhibited CO2 production from all tested substrates, as well as the respiratory chain complex IV activity. The other activities of the respiratory chain were not affected by these metabolites. The data indicate a marked blockage in the Krebs cycle and a mild inhibition of the respiratory chain caused by MAA and MHB. Furthermore, MHB inhibited total and mitochondrial creatine kinase activities, which was prevented by the use of the nitric-oxide synthase inhibitor L-NAME and glutathione (GSH). These data indicate that the effect of MHB on creatine kinase was probably mediated by oxidation or other modification of essential thiol groups of the enzyme by nitric oxide and other by-products derived from this organic acid. In contrast, MAA did not affect creatine kinase activity. Taken together, these observations indicate that aerobic energy metabolism is inhibited by MAA and to a greater extent by MHB, a fact that may be related to lactic acidaemia occurring in patients affected by MHBD and beta-ketothiolase deficiencies. If the in vitro effects detected in the present study also occur in vivo, it is tempting to speculate that they may contribute, at least in part, to the neurological dysfunction found in these disorders.
Assuntos
Acetoacetatos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/embriologia , Metabolismo Energético , Hidroxibutiratos/farmacologia , 3-Hidroxiacil-CoA Desidrogenases , Acetatos/metabolismo , Acetil-CoA C-Aciltransferase/metabolismo , Acidose/metabolismo , Oxirredutases do Álcool/metabolismo , Animais , Encéfalo/metabolismo , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Córtex Cerebral/metabolismo , Citratos/metabolismo , Creatina Quinase/metabolismo , Relação Dose-Resposta a Droga , Transporte de Elétrons , Glucose/metabolismo , Glutationa/metabolismo , Glicina/análogos & derivados , Glicina/metabolismo , Técnicas In Vitro , Deficiência Intelectual , Ácido Láctico/metabolismo , NG-Nitroarginina Metil Éster/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Oxigênio/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
We have studied the developmental changes of glucose, mannose, fructose and galactose metabolism in rat cerebral cortex. As the animals aged, glucose, mannose and fructose oxidation to CO2 increased, whereas galactose oxidation decreased. Lipid synthesis from glucose and fructose also increased with age, that from mannose decreased and galactose did not change. Cytochalasin B, a potent non-competitive inhibitor of sodium-independent glucose transport, significantly impaired glucose, mannose and galactose metabolism, but had no effect on fructose metabolism. Both galactose or fructose did not change, whereas mannose declined the glucose metabolism. Glucose decreased fructose, galactose and mannose metabolism. Our results show that besides glucose, the metabolism of mannose, galactose and fructose present developmental changes from fetal to adult age, and reinforce the literature data indicating that mannose and galactose are transported by glucose carriers, while fructose is not.
Assuntos
Envelhecimento/metabolismo , Córtex Cerebral/enzimologia , Hexoses/metabolismo , Animais , Dióxido de Carbono/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/crescimento & desenvolvimento , Citocalasina B/farmacologia , Relação Dose-Resposta a Droga , Lipídeos/biossíntese , Oxirredução/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The aim of this study was to investigate the possible involvement of the glutamatergic system in the toxicity of organochalcogens, since this is an important neurotransmitter system for signal transduction and neural function. The results indicated that 100 microM diphenyl diselenide (PhSe)(2) and diphenyl ditelluride (PhTe)(2) inhibit by 50 and 70% (P<0.05), respectively, [(3)H]glutamate binding in vitro. Acute administration of 25 micromol/kg (PhSe)(2) or 3 micromol/kg (PhTe)(2) caused a significant reduction in [(3)H]glutamate (30%, P<0.05) or [(3)H]MK-801 binding (30%, P<0.05) to rat synaptic membranes. These results suggest that (PhSe)(2) and (PhTe)(2) affect, in a rather complex way, the glutamatergic system after acute in vivo exposure in rats. In vitro, total [(3)H]GMP-PNP binding was inhibited about 40% at 100 microM (PhSe)(2) and (PhTe)(2). Acute exposure in vivo to (PhSe)(2) decreased the stable [(3)H]GMP-PNP binding to 25% and (PhTe)(2) to 68% of the control value (P<0.05, for both compounds). Simultaneously, the unstable binding of [(3)H]GMP-PNP was decreased about 30 and 50% (P<0.05, for both compounds) after exposure to (PhSe)(2) and (PhTe)(2), respectively. GMP-PNP stimulated adenylate cyclase (AC) activity significantly in control animals. (PhSe)(2)- and (PhTe)(2)-treated animals increased the basal activity of this enzyme, but GMP-PNP stimulation was totally abolished. These results suggest that the toxic effects of organochalcogens could result from action at different levels of neural signal transduction pathways, possibly involving other neurotransmitters besides the glutamatergic system.
Assuntos
Derivados de Benzeno/toxicidade , Encéfalo/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Compostos Organometálicos/toxicidade , Compostos Organosselênicos/toxicidade , Terminações Pré-Sinápticas/efeitos dos fármacos , Membranas Sinápticas/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Telúrio/toxicidade , Animais , Ligação Competitiva/efeitos dos fármacos , Ligação Competitiva/fisiologia , Encéfalo/metabolismo , Ditiotreitol/farmacocinética , Maleato de Dizocilpina/farmacocinética , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacocinética , Ácido Glutâmico/farmacocinética , Guanilil Imidodifosfato/farmacocinética , Masculino , Neurotoxinas/farmacologia , Terminações Pré-Sinápticas/metabolismo , Ratos , Ratos Wistar , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Membranas Sinápticas/metabolismo , Transmissão Sináptica/fisiologia , Trítio/farmacocinéticaRESUMO
It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 microCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.
Assuntos
Dióxido de Carbono/metabolismo , Córtex Cerebral/metabolismo , Glucose/metabolismo , Hipocampo/metabolismo , Estresse Fisiológico/metabolismo , Doença Aguda , Animais , Glicemia/análise , Doença Crônica , Corticosterona/sangue , Masculino , Oxirredução , Ratos , Ratos WistarRESUMO
It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 æCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells
Assuntos
Animais , Masculino , Ratos , Dióxido de Carbono/metabolismo , Córtex Cerebral/metabolismo , Glucose/metabolismo , Hipocampo/metabolismo , Estresse Fisiológico/metabolismo , Doença Aguda , Glicemia/análise , Doença Crônica , Corticosterona/sangue , Oxirredução , Ratos WistarRESUMO
BACKGROUND/AIMS: Undernutrition reduces the hypothalamic ganglioside concentration. This may be attributed to some modifications in the contents of precursors of sphingolipid biosynthesis in undernourished rats. The present study evaluated the serine palmitoyl transferase activity (SPT; EC 2.3.1.50) during the development of the rat hypothalamus. This work also shows the L-[3-(14)C]serine metabolic labeling of hypothalamic sphingolipids in normal and undernourished rats at weaning. METHODS: The SPT activity was determined in microsomal fractions obtained from the hypothalamus of normal rats (diet: 25% protein) and pre- and postnatally undernourished rats (diet: 8% protein since pregnancy) at 21 days of gestational age and at 7, 14, and 21 days of postnatal life. RESULTS: The enzymatic activity was lower in the hypothalamus of undernourished than in the hypothalamus of control rats since the 7th postnatal day. Incorporation of the precursor L-[3-(14)C]serine into sphingolipid fraction was lower in the hypothalamus of undernourished rats than in the hypothalamus of control rats on the 21st postnatal day which coincided with the age of the highest difference in SPT activity between normal and undernourished rats. CONCLUSION: These results indicate that undernutrition reduces the biosynthesis of the main sphingolipids during the period of brain growth spurt.
Assuntos
Aciltransferases/metabolismo , Antígenos CD , Hipotálamo/enzimologia , Hipotálamo/crescimento & desenvolvimento , Distúrbios Nutricionais/enzimologia , Animais , Autorradiografia , Radioisótopos de Carbono , Feminino , Gangliosídeos/metabolismo , Glucosilceramidas/metabolismo , Lactosilceramidas/metabolismo , Ratos , Ratos Wistar , Serina/metabolismo , Serina C-Palmitoiltransferase , Esfingomielinas/metabolismoRESUMO
We studied protein synthesis, lipid synthesis and CO2 production by oxidation of glycine, alanine and leucine by slices of rat hippocampus during the period of brain growth spurt. The metabolism of the three amino acids decreased with the age of the animals. A major reduction was observed in protein synthesis, which was 4 times higher at 7 days of age than at 21 days of age for all amino acids studied. Glycine oxidation to CO2 was twice as high as alanine oxidation and ten times higher than leucine oxidation. The major pathway of leucine utilization was incorporation into proteins. Glycine was the amino acid that had the highest metabolic rate.
Assuntos
Alanina/metabolismo , Metabolismo Energético/fisiologia , Glicina/metabolismo , Hipocampo/fisiologia , Leucina/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Animais , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Técnicas In Vitro , Lipídeos/biossíntese , Ratos , Ratos WistarRESUMO
Female Wistar rats were fed a low-soybean protein (8%) diet supplemented with different concentrations of DL-methionine (0-1.2%) during the lactation period. Diet supplementation with methionine caused a significant increase in rat body weight. The addition of 0.3% DL-methionine to the diet did not cause an increase in liver triacylglycerol concentration in 21-day-old rats, but an increase did occur after the addition of 0.6% DL-methionine to the diet. Supplementation of the diet with DL-methionine did not change liver phospholipid or protein concentrations, nor plasma triacylglycerol levels. Liver lipid synthesis from [1-14C]acetate in 21-day-old rats whose dams had been fed an 8% soybean protein diet supplemented with 1.2% DL-methionine was significantly higher than in the group receiving no DL-methionine supplementation. Hepatic production of CO2 and of water-soluble acid products from [1-14C]palmitate did not differ between groups. Inositol addition to a low-soybean protein diet supplemented with DL-methionine did not change triacylglycerol nor phospholipid levels in the liver.
Assuntos
Proteínas Alimentares/farmacologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Metionina/farmacologia , Proteínas de Vegetais Comestíveis/farmacologia , Acetatos/metabolismo , Animais , Radioisótopos de Carbono , Feminino , Alimentos Fortificados , Lactação/fisiologia , Fígado/química , Fígado/efeitos dos fármacos , Palmitatos/metabolismo , Fosfolipídeos/análise , Fosfolipídeos/sangue , Distribuição Aleatória , Ratos , Ratos Wistar , Proteínas de Soja , Glycine max , Triglicerídeos/análise , Triglicerídeos/sangueRESUMO
Total ganglioside and sialoglycoprotein concentrations were determined in the hypothalamus of normal (diet: 25% casein), postnatal undernourished (diet: 8% casein since birth), and pre- and postnatal undernourished rats (diet: 8% casein since pregnancy). Hypothalamic weights for the two low protein diet groups were lower than for the normal diet groups at all ages studied. Total hypothalamic ganglioside and sialoglycoproteins (mumol NANA) of postnatal undernourished rats were lower than control at day 10, while in pre- and postnatal undernourished rats this difference occurred at day 7. The reduction in gangliosides and sialoglycoprotein contents was not solely a consequence of the decrease in hypothalamic weight since, when the data were expressed as nmol NANA/mg tissue, similar reductions were observed principally in the pre- and postnatal protein undernutrition group. These results suggest that the effects of pre- and postnatal undernutrition on hypothalamic gangliosides and sialoglycoproteins are more pronounced than those that occur as a result of postnatal undernutrition.
Assuntos
Gangliosídeos/metabolismo , Hipotálamo/metabolismo , Desnutrição Proteico-Calórica/metabolismo , Sialoglicoproteínas/metabolismo , Envelhecimento/metabolismo , Animais , Peso Corporal/fisiologia , Feminino , Tamanho do Órgão/fisiologia , Gravidez , RatosRESUMO
Female Wistar rats were fed a normal-protein diet (25% casein) or a low-protein diet (8% casein) during pregnancy and lactation. The two diets were isocaloric and contained appropriate amounts of mineral salts and vitamins. Pups from dams submitted to the low-protein diet had a lower body weight than normally fed controls as early as on the day of birth, but a difference in cerebellar weight between the two groups was observed only on the 15th postnatal day. Malnutrition had no effect on cerebellar protein concentration, which increased with age in both groups. The cerebellar DNA concentration was higher at 7 and 15 days of age in normally fed rats than in malnourished rats, whereas at 21 days of age it was higher in the malnourished animals. [U-14C]Leucine and [2-3H]mannose incorporation into proteins and lipid synthesis from acetyl coenzyme A (CoA) derived from [U-14C]leucine markedly decreased with age in the cerebellum of rats fed both diets. [2-3H]Mannose incorporation into cerebellar glycoproteins was greater in malnourished rats during the period of brain growth spurt than in normally fed rats at all ages studied. Prenatal and postnatal protein malnutrition had no effect on [U-14C]leucine incorporation into cerebellar proteins or on cerebellar lipid synthesis from acetyl-CoA derived from [U-14C]leucine during the period of brain growth spurt.
Assuntos
Cerebelo/crescimento & desenvolvimento , Glicoproteínas/biossíntese , Lipídeos/biossíntese , Distúrbios Nutricionais/metabolismo , Biossíntese de Proteínas , Fatores Etários , Animais , Animais Recém-Nascidos/metabolismo , Cerebelo/metabolismo , DNA/metabolismo , Proteínas Alimentares/administração & dosagem , Feminino , Distúrbios Nutricionais/fisiopatologia , Ratos , Ratos EndogâmicosRESUMO
The testes of 40-day-old rats subjected to protein malnutrition show a marked delay in maturation of the seminiferous epithelium, as well as greater mannose incorporation into glycoprotein than observed in normal animals of the same age. Testes were incubated for 1 h with [2-3H]mannose and germ cells were then separated by the Staput method. Mannose incorporation occurred in the same cell fraction, i.e. the spermatocytes, both in normally fed and protein-undernourished animals. These data were confirmed by incubating the cells previously isolated on the gradient with [2-3H]mannose. Comparison of these data with results obtained in previous studies on 20-day-old animals in which mannose incorporation was lower in undernourished rats suggests that the differences observed in the present study between the experimental groups are due to alterations in the germ cells.
Assuntos
Glicoproteínas/biossíntese , Deficiência de Proteína/metabolismo , Testículo/metabolismo , Animais , Peso Corporal , Separação Celular , Células Germinativas/metabolismo , Masculino , Tamanho do Órgão , Deficiência de Proteína/patologia , Ratos , Ratos Endogâmicos , Testículo/crescimento & desenvolvimento , Testículo/patologiaRESUMO
Rats raised and maintained on a normal-protein diet (25% protein) responded to the ip administration of ACTH-(1-24), epinephrine or Met-enkephalin with a decrease in hypothalamic beta-endorphin-like immunoreactivity, which is attributable to a release of this substance. This effect was not seen in rats raised and maintained on a low-protein diet (8% protein). In the normal animals, the pre-test administration of ACTH, epinephrine or Met-enkephalin and the post-training administration of naloxone enhanced retention-test performance of a step-down inhibitory avoidance task. These behavioral effects were absent in the protein-malnourished rats. Previous studies have shown that the behavioral effect of post-training naloxone is secondary to the release of brain beta-endorphin during training, and that the pre-test effect of the hormones is due to a release of brain beta-endorphin induced by the substances themselves. Since it is not likely that the differences were caused by hyperreactivity to the aversive stimuli employed, the suggested interpretation is that protein-malnourished rats present a dysfunction in the brain beta-endorphin system which renders it unresponsive not only to novel training experiences, but also to the pre-test retrieval enhancing effects of ACTH, epinephrine and Met-enkephalin.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/metabolismo , Encefalina Metionina/farmacologia , Epinefrina/farmacologia , Memória/efeitos dos fármacos , Desnutrição Proteico-Calórica/metabolismo , Retenção Psicológica/efeitos dos fármacos , beta-Endorfina/metabolismo , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/farmacologia , Encefalina Metionina/administração & dosagem , Epinefrina/administração & dosagem , Feminino , Injeções Intraperitoneais , Gravidez , Ratos , Ratos EndogâmicosRESUMO
Rats raised and maintained on a normal-protein diet (25% protein) responded to the ip adminsitration of ACTH-(1-24), epinephrine or Met-enkephalin with a decrease in hypothalamic Beta-endorphin-like immunoreactivity, which is attributable to a release of this substance. This effect was not seen in rats raised an maintained on a low-protein diet (8% protein). In the normal animals, the pre-test administration of ACTH, epinephrine or Met-enkephalin and the post-training adminsitration of naloxone enhanced retention-test performance of a step-down inhibitory avoidance task. These behavioral effects were absent in the protein-malnourished rats. Previous studies have shown that the behavioral effect of post-training naloxone is secondary to the release of brain Beta-endorphin during training, and that the pre-test it is not likely that the differences were caused by hyperreactivity to the aversive stimuli employed, the suggested interpretation is that protein-malnourished rats present a dysfunction in the brain Beta-endorphin system which renders it unresponsive not only to novel training experiences, but also to the pre-test retrieval enchancing effects of ACTH, epinephrine and Met-enkephalin
Assuntos
Gravidez , Ratos , Animais , Feminino , Hormônio Adrenocorticotrópico/administração & dosagem , Aprendizagem da Esquiva/efeitos dos fármacos , beta-Endorfina/metabolismo , Cérebro/metabolismo , Encefalina Metionina/administração & dosagem , Epinefrina/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ratos EndogâmicosRESUMO
Rats were submitted to a normal (25% casein) or a low protein diet (8% casein) from the day of birth until the age of 110 to 120 days. Hypothalamic beta-endorphin-like immunoreactivity was lower in the animals raised and maintained with the low protein diet, and, in addition, it did not respond to training in a step-down inhibitory avoidance task with or without footshock with a depletion, as was the case with the normal diet animals. In the animals submitted to the normal protein diet posttraining ACTH (0.2 micrograms/kg) and beta-endorphin (1.0 micrograms/kg) caused retrograde amnesia of a step-down inhibitory avoidance task, and pretest administration of these substances had no effect of its own, but was able to reverse the amnesia induced by their previous posttraining administration. In the animals submitted to the low protein diet, results were similar except that pretest beta-endorphin caused amnesia on its own. On the basis of previous findings which suggest that pretest actions of ACTH and beta-endorphin depend on their endogenous release at the time of training, the present results are compatible with a malfunction of the brain beta-endorphin system in the undernourished animals.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Desnutrição Proteico-Calórica/fisiopatologia , beta-Endorfina/farmacologia , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Dieta , Hipotálamo/análise , Masculino , Radioimunoensaio , Ratos , Ratos Endogâmicos , Retenção Psicológica/efeitos dos fármacos , Fatores de Tempo , beta-Endorfina/administração & dosagem , beta-Endorfina/análiseRESUMO
Pregnant Wistar rats were fed ad libitum diets containing either 25% (control) or 8% casein (undernourished) from conception through the gestation and lactation periods. Rats from undernourished dams had lower birth weights than control rats and this difference persisted up to day 21 of postnatal life. Livers obtained from undernourished animals aged 10, 15 and 20 days weighed 50% less than control livers. Liver glycogen concentration was much higher in 7- and 10-day-old undernourished rats than in normal rats, but no differences were observed between groups aged 15 or 20 days. Malnutrition caused a decrease in glycemia from 10 days of age and an increase in ketonemia at 10 and 15 days of age. The results show that pre- and postnatal protein malnutrition causes changes in carbohydrate and lipid metabolism in rats during the period of brain growth spurt.