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
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
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