Efeitos de dietas hiperlipídicas sobre a oxidação da glicose em tecido adiposo : participação da adenosina

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Efeitos do hipotireoidismo e hipertireoidismo durante a lactação sobre a atividade da enzima ALA-D em sangue e fígado de ratos wistar

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Cerebral ketone body oxidation is facilitated by a high fat diet enriched with advanced glycation end products in normal and diabetic rats

Diabetesmellitus(DM)causesimportantmodificationsintheavailabilityanduseofdifferentenergysubstratesinvariousorgansandtissues.Similarly,dietarymanipulationssuchashighfatdietsalsoaffectsystemicenergymetabolism.However,howthebrainadaptstothesesituationsremainsunclear.Toinvestigatetheseissues,controlandalloxan-inducedtypeIdiabeticratswerefedeitherastandardorahighfatdietenrichedwithadvancedglycationendproducts(AGEs)(HAGEdiet).TheHAGEdietincreasedtheirlevelsofbloodketonebodies,andthiseffectwasexacerbatedbyDMinduction.Todeterminetheeffectsofdietand/orDMinductiononkeycerebralbioenergeticparameters,bothketonebodies(b-hydroxybutyricacid)andlactateoxidationweremeasured.Inparallel,theexpressionofMonocarboxylateTransporter1(MCT1)and2(MCT2)isoformsinhippocampalandcorticalslicesfromratssubmittedtothesedietswasassessed.KetonebodyoxidationincreasedwhilelactateoxidationdecreasedinhippocampalandcorticalslicesinbothcontrolanddiabeticratsfedaHAGEdiet.Inparallel,theexpressionofbothMCT1andMCT2increasedonlyinthecerebralcortexindiabeticratsfedaHAGEdiet.TheseresultssuggestashiftinthepreferentialcerebralenergysubstrateutilizationinfavorofketonebodiesinanimalsfedaHAGEdiet,aneffectthat,inDManimals,isaccompaniedbytheenhancedexpressionoftherelatedtransporters

Can glutathione be a biomarker for suicide risk in women 18 months postpartum?

Background: Suicide risk is prominent among the problems affecting populations, mainly due to the broad family, psychosocial and economic impact. Most individuals at suicidal risk have some mental disorder. There is considerable evidence that psychiatric disorders are accompanied by the activation of neuro-immune and neuro-oxidative pathways. The aim of the study is to evaluate the serum levels of oxidative stress biomarkers in women at risk of suicide after 18 months of postpartum. Methods: This is a case-control study, nested within a cohort study. From this cohort, 45 women [15 without mood disorders and 30 with mood disorders (Major depression and Bipolar disorder)] were selected at 18 months postpartum, the depression and suicide risk were assessed using the MiniInternational Neuropsychiatric Interview Plus (MINI-Plus) instrument, module A and C, respectively. Blood was collected and stored for later analysis of the reactive species (DCFH), superoxide dismutase (SOD), and glutathione reduced (GSH). For data analysis, the SPSS program was used. To compare the nominal covariates with the outcome GSH levels, the Student’s t-test or analysis of variance (ANOVA) was used. Spearman’s correlation was performed for analysis between the quantitative covariates and the outcome. To analyze the interaction between the factors, multiple linear regression was performed. Bonferroni analysis was used as an additional/secondary result to visualize differences in glutathione levels according to risk severity. After the adjusted analysis, p-values < 0.05 were considered statistically significant. Results: The percentage of suicide risk observed in our sample of women at 18 months postpartum was 24.4% (n = 11). After adjusting for the independent variables, only the presence of suicide risk remained associated with the outcome (β = 0.173; p = 0.007), low levels of GSH at 18 months after postpartum. Likewise, we verified the difference in GSH levels according to the degree of suicide risk, observing a significant association between the differences in glutathione means in the group of women with moderate to high risk compared to the reference group (no suicide risk) (p = 0.009). Conclusion: Our findings suggest that GSH may be a potential biomarker or etiologic factor in women at moderate to high risk of suicide

Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with Advanced Glycation End Products in Normal and Diabetic Rats.

Diabetes mellitus (DM) causes important modifications in the availability and use of different energy substrates in various organs and tissues. Similarly, dietary manipulations such as high fat diets also affect systemic energy metabolism. However, how the brain adapts to these situations remains unclear. To investigate these issues, control and alloxan-induced type I diabetic rats were fed either a standard or a high fat diet enriched with advanced glycation end products (AGEs) (HAGE diet). The HAGE diet increased their levels of blood ketone bodies, and this effect was exacerbated by DM induction. To determine the effects of diet and/or DM induction on key cerebral bioenergetic parameters, both ketone bodies (β-hydroxybutyric acid) and lactate oxidation were measured. In parallel, the expression of Monocarboxylate Transporter 1 (MCT1) and 2 (MCT2) isoforms in hippocampal and cortical slices from rats submitted to these diets was assessed. Ketone body oxidation increased while lactate oxidation decreased in hippocampal and cortical slices in both control and diabetic rats fed a HAGE diet. In parallel, the expression of both MCT1 and MCT2 increased only in the cerebral cortex in diabetic rats fed a HAGE diet. These results suggest a shift in the preferential cerebral energy substrate utilization in favor of ketone bodies in animals fed a HAGE diet, an effect that, in DM animals, is accompanied by the enhanced expression of the related transporters

Efeitos das glicotoxinas sobre o metabolismo energético do sistema nervoso central e o estado redox no sistema periférico de ratos : possíveis efeitos prejudicais do diabetes e benéficos do ácido graxo poli-insaturado omega 3

Durante as últimas décadas a incidência de obesidade e diabetes tipo 2 vem aumentando assustadoramente, principalmente, em crianças. Recentes estudos sugerem que a hiperglicemia crônica, situação comum em diabéticos sem controle sobre a glicemia, altera mecanismos intracelulares, incluindo aumento na via dos polióis, ativação da proteína quinase C, aumento da via das hexosaminas e aumento na formação de produtos finais da glicação avançada (AGEs). Complicações vasculares como a nefropatia e a neuropatia são comumente encontradas em pacientes diabéticos, assim como falha na função cardíaca e hepática. Os AGEs estão relacionados com o aumento de: estresse oxidativo, dano ao ADN, citocinas pró-inflamatórias e resistência à insulina. Nos últimos anos muitas drogas têm sido testadas para prevenção ou diminuição dos efeitos das glicotoxinas, principalmente no diabetes, entretanto poucas obtiveram sucesso. Na presente tese, demonstramos que as glicotoxinas endógenas e exógenas afetam o metabolismo de alguns aminoácidos e o metabolismo energético do sistema nervoso central de maneira a prejudicar sua homeostase. Podemos concluir, também, que os Ω3- PUFAs demonstraram melhorar o estado redox no fígado e no rim de ratos diabéticos alimentados com uma dieta hiperlipídica aquecida. Estes resultados podem sugerir que os ácidos graxos poli-insaturados Omega 3 (Ω3-PUFAs) possam ser adjuvante no tratamento de algumas doenças como diabetes mellitus e resistência à insulina.During the last decades the incidence of obesity and type 2 diabetes has increased alarmingly, especially in children. Some studies suggest that chronic hyperglycemia, a situation common in diabetics with no control over blood glucose levels, alters intracellular mechanisms, including increased polyol pathway, activation of protein kinase C, increased of Hexosamines pathway and increased formation of advanced glycation end products (AGEs). Vascular complications such as nephropathy and neuropathy are commonly found in diabetic patients, as well as cardiac and liver failure. AGEs are related to the increase: oxidative stress, DNA damage, proinflammatory cytokines and insulin resistance. In recent years several drugs have been tested for preventing or mitigating the effects of glycotoxins, especially in diabetes, but few have succeeded. In this thesis, we demonstrate that endogenous and exogenous glycotoxins affect metabolism of some amino acids and energy metabolism of the central nervous system in a manner detrimental homeostasis. We can also conclude that Ω3-PUFAs shown to improve the redox state in liver and kidney of diabetic rats fed a heated fat diet. These results may suggest that polyunsaturated fatty acids Omega 3 (Ω3-PUFAs) can be used as adjuvant in the treatment of some diseases such as diabetes mellitus and insulin resistance

Efeitos da dieta hieperlipídica aquecida e dieta hiperlipídica normal na formação de produtos finais de glicação avançada e de espécies reativas de oxigênio em ratos Wistar

O dano ao ADN pode estar associado com o diabetes mellitus tipo II (T2DM) e suas complicações, incluindo estresse oxidativo. Os parâmetros bioquímicos relacionados com o metabolismo glicídico (glicose, insulina, TTG e TSI) e parâmetros corporais (peso corporal, tecido adiposo) foram avaliados após 12 meses de tratamento com dieta hiperlipídica e dieta hiperlipídica aquecida. Após o período experimental, os ratos tratados com dietas hiperlipídicas obtiveram aumento de peso corporal e aumento de glicemia e insulinemia quando comparado ao grupo controle normolipídico. A dieta hiperlipídica (HFD) e a dieta hiperlipídica aquecida (HFTD) também levaram a uma redução na sensibilidade à insulina e na tolerância à glicose, independentemente dos tempos estudados. Interessantemente, somente os animais submetidos à dieta aquecida demonstraram redução na oxidação de glicose pelo tecido adiposo epididimal. Mostramos que ambas as dietas hiperlipídicas tem a capacidade de reduzir a síntese de glicogênio pelas vias, direta e indireta. A dieta aquecida acarretou um aumento significativo na peroxidação lipídica no fígado em relação aos demais grupos. Utilizando o ensaio cometa, verificamos um aumento significativo de dano ao ADN em sangue e hipocampo dos ratos submetidos às dietas hiperlipídicas, tendo o grupo HFTD aumento maior em relação ao HFD. Estes resultados sugerem que uma correlação positiva entre dieta hiperlipídica, alteração no metabolismo glicídico, estresse oxidativo e dano ao ADN. Contudo, o aquecimento da dieta parece agravar tais resultados.Many studies have demonstrated that DNA damage may be associated with type 2 diabetes mellitus (T2DM) and its complications. The goal of this study was to evaluate the effects of the potential relationship between fat (thermolyzed) intake, glucose dyshomeostasis and DNA injury in rats. Biochemical parameters related to glucose metabolism (i.e., blood glucose levels, insulin tolerance tests, glucose tolerance tests and fat cell glucose oxidation) and general health parameters (i.e., body weight, retroperitoneal and epididymal adipose tissue) were evaluated in rats after a 12-month treatment with either a high fat or a high thermolyzed fat diet. The high fat diet (HFD) and high fat thermolyzed diet (HFTD) showed increased body weight and impaired insulin sensitivity at the studied time-points in insulin tolerance test (ITT) and glucose tolerance test (GTT). Interestingly, only animals subjected to the HFTD diet showed decreased epididymal fat cell glucose oxidation. We show which high fat diets have the capacity to reduce glycogen synthesis by direct and indirect pathways. HFTD promoted an increase in lipid peroxidation in the liver, demonstrating significant damage in lipids in relation to other groups. Blood and hippocampus DNA damage was significantly higher in animals subjected to HFDs, and the highest damage was observed in animals from the HFTD group. Striatum DNA damage was significantly higher in animals subjected to HFDs, compared with the control group. These results show a positive correlation between high fat diet, glucose dyshomeostasis, oxidative stress and DNA damage

Efeitos das glicotoxinas sobre o metabolismo energético do sistema nervoso central e o estado redox no sistema periférico de ratos : possíveis efeitos prejudicais do diabetes e benéficos do ácido graxo poli-insaturado omega 3

Durante as últimas décadas a incidência de obesidade e diabetes tipo 2 vem aumentando assustadoramente, principalmente, em crianças. Recentes estudos sugerem que a hiperglicemia crônica, situação comum em diabéticos sem controle sobre a glicemia, altera mecanismos intracelulares, incluindo aumento na via dos polióis, ativação da proteína quinase C, aumento da via das hexosaminas e aumento na formação de produtos finais da glicação avançada (AGEs). Complicações vasculares como a nefropatia e a neuropatia são comumente encontradas em pacientes diabéticos, assim como falha na função cardíaca e hepática. Os AGEs estão relacionados com o aumento de: estresse oxidativo, dano ao ADN, citocinas pró-inflamatórias e resistência à insulina. Nos últimos anos muitas drogas têm sido testadas para prevenção ou diminuição dos efeitos das glicotoxinas, principalmente no diabetes, entretanto poucas obtiveram sucesso. Na presente tese, demonstramos que as glicotoxinas endógenas e exógenas afetam o metabolismo de alguns aminoácidos e o metabolismo energético do sistema nervoso central de maneira a prejudicar sua homeostase. Podemos concluir, também, que os Ω3- PUFAs demonstraram melhorar o estado redox no fígado e no rim de ratos diabéticos alimentados com uma dieta hiperlipídica aquecida. Estes resultados podem sugerir que os ácidos graxos poli-insaturados Omega 3 (Ω3-PUFAs) possam ser adjuvante no tratamento de algumas doenças como diabetes mellitus e resistência à insulina.During the last decades the incidence of obesity and type 2 diabetes has increased alarmingly, especially in children. Some studies suggest that chronic hyperglycemia, a situation common in diabetics with no control over blood glucose levels, alters intracellular mechanisms, including increased polyol pathway, activation of protein kinase C, increased of Hexosamines pathway and increased formation of advanced glycation end products (AGEs). Vascular complications such as nephropathy and neuropathy are commonly found in diabetic patients, as well as cardiac and liver failure. AGEs are related to the increase: oxidative stress, DNA damage, proinflammatory cytokines and insulin resistance. In recent years several drugs have been tested for preventing or mitigating the effects of glycotoxins, especially in diabetes, but few have succeeded. In this thesis, we demonstrate that endogenous and exogenous glycotoxins affect metabolism of some amino acids and energy metabolism of the central nervous system in a manner detrimental homeostasis. We can also conclude that Ω3-PUFAs shown to improve the redox state in liver and kidney of diabetic rats fed a heated fat diet. These results may suggest that polyunsaturated fatty acids Omega 3 (Ω3-PUFAs) can be used as adjuvant in the treatment of some diseases such as diabetes mellitus and insulin resistance