RESUMO
AIM: Obesity is a worldwide health issue, associated with development of type 2 Diabetes Mellitus. The aim of this study is to analyze the effect of consumption of two hypercaloric diets on metabolic disturbance and beta cells damage. MAIN METHODS: Male Wistar rats were subjected to twelve months consumption of three diets: a Control balanced diet (CTD, carbohydrates 58 %, proteins 29 %, lipids 13 %) and two hypercaloric diets, high in sucrose (HSD, carbohydrates 68 %, proteins 22 %, lipids 10 %) or high in fat (HFD, carbohydrates 31 %, proteins 14 %, lipids 55 %). Serum levels of glucose, triglycerides and free fatty acids were measured after zoometric parameters determination. Antioxidant enzymes activity and oxidative stress-marker were measured in pancreas tissue among histological analysis of Langerhans islets. KEY FINDINGS: Although diets were hypercaloric, the amount of food consumed by rats decreased, resulting in an equal caloric consumption. The HSD induced hypertriglyceridemia and hyperglycemia with higher levels in free fatty acids (FFA, lipotoxicity); whereas HFD did not increased neither the triglycerides nor FFA, nevertheless the loss of islets' cell was larger. Both diets induced obesity with hyperglycemia and significant reduction in Langerhans islets size. SIGNIFICANCE: Our results demonstrate that consumption of HSD induces more significant metabolic disturbances that HFD, although both generated pancreas damage; as well hypercaloric diet consumption is not indispensable to becoming obese; the chronic consumption of unbalanced diets (rich in carbohydrates or lipids) may lead to abdominal obesity with metabolic and functional disturbances, although the total amount of calories are similar.
Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Masculino , Ratos , Animais , Diabetes Mellitus Tipo 2/etiologia , Obesidade Abdominal/etiologia , Sacarose , Ácidos Graxos não Esterificados , Células de Langerhans/metabolismo , Ratos Wistar , Glicemia/metabolismo , Obesidade/metabolismo , Dieta , Triglicerídeos/metabolismo , Dieta Hiperlipídica/efeitos adversosRESUMO
Identification of new modifications and the association with diet patterns are essential for the prevention of non-alcoholic fatty liver disease (NAFLD). To address this problem, we feed rats with high caloric diets based on high sucrose (HSD) and high fat (HFD) and analysed metabolic and mitochondrial alterations. Both diets induce moderated obesity and fat accumulation in the liver after 8, 10 and 12 months of diet. The HSD induces both hyperleptinemia and hyperinsulinemia, as well as up-regulation of transcription factors SRBEP1 and PPARγ along slight increase nitrosylation of proteins and increased mitochondrial fission. In contrast, HFD induced hyperleptinemia without changes in neither insulin levels nor oxidative stress, SREBP1, PPARγ, or mitochondrial dynamics. In conclusion, chronic consumption of high sucrose content diets induces more pathological and metabolic alteration in liver in comparison with consumption of high-fat content diets, although both induces obesity and liver steatosis in these animal models.
Assuntos
Dinâmica Mitocondrial , Hepatopatia Gordurosa não Alcoólica , Animais , Ratos , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/metabolismo , PPAR gama/metabolismo , Sacarose/metabolismo , Açúcares/metabolismo , Regulação para CimaRESUMO
Previous studies have proposed that the human papillomavirus (HPV) E6 oncoproteins modify the transcriptional activity of eIF4E through mechanisms dependent on p53 degradation. However, the effect of these oncoproteins on pathways regulating the activity of the eIF4E protein remains poorly understood. Hence, we investigated the mechanisms whereby E6 proteins regulate the activity of the eIF4E protein and its effect on target genes. Overexpression of E6 constructs (HPV-6, HPV-16, HPV-18, and HPV52) showed that E6 oncoproteins increased phosphorylation of the eIF4E protein (Serine-209). This result was mainly mediated by phosphorylation of the 4EBP1 protein via the PI3K/AKT pathway. Additionally, the pharmacological inhibition of eIF4E phosphorylation in cervical cancer cell lines substantially reduced the protein levels of CCND1 and ODC1, indicating that E6 of the high-risk genotypes may modify protein synthesis of the eIF4E target genes by increasing the activity of the AKT and ERK pathways.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Fator de Iniciação 4E em Eucariotos/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Proteínas Repressoras/metabolismo , Células Cultivadas , Feminino , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoAssuntos
Coinfecção/epidemiologia , Infecções por Mycoplasma/epidemiologia , Mycoplasma/isolamento & purificação , Papillomaviridae/isolamento & purificação , Lesões Pré-Cancerosas/epidemiologia , Infecções por Ureaplasma/epidemiologia , Ureaplasma/isolamento & purificação , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Genótipo , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Mycoplasma/classificação , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/microbiologia , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Prevalência , Ureaplasma/classificação , Infecções por Ureaplasma/diagnóstico , Infecções por Ureaplasma/microbiologiaRESUMO
Introduction. Bacterial vaginosis (BV) is dysbiosis associated with an increased risk of several sexually transmitted infections. It is primarily diagnosed via Gram staining, although molecular analyses have presented higher diagnostic accuracy.Aim. This study aimed to evaluate the molecular epidemiology of BV in asymptomatic women to determine its association with several commensal and pathogenic micro-organisms of the genitalia.Methodology. The prevalence of BV was investigated through semiquantitative assessment of 201 women recruited during their routine gynaecological inspection at an outpatient clinic in Tabasco, Mexico.Results. Women with BV showed an increased prevalence of Chlamydia trachomatis (P=0.021) and Mycoplasma hominis (P=0.001). Of the BV-associated micro-organisms, Gardnerella vaginalis was significantly associated with C. trachomatis (P=0.005) and/or Ureaplasma parvum (P=0.003), whereas Atopobium vaginae and Megasphaera type 1 correlated significantly with Mycoplasma hominis (P=0.001). No significant association was observed between human papillomavirus (HPV) infection and BV, although there was increased prevalence of HPV59, HPV73, HPV52 and HPV58 in women displaying cervical cytological abnormalities.Conclusion. Identification of BV-associated micro-organisms via molecular analysis may help to distinguish recurrent cases from new infections and identify micro-organisms potentially associated with pharmacological resistance.
Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Genitália Feminina/microbiologia , Epidemiologia Molecular , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/microbiologia , Adolescente , Adulto , Doenças Assintomáticas , Bactérias/genética , Feminino , Genitália Feminina/virologia , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Prevalência , Adulto JovemRESUMO
BACKGROUND: Functional receptors for leptin were described on the surface of cardiomyocytes, and there was a prohypertrophic effect with high concentrations of the cytokine. Therefore, leptin could be a link between obesity and the prevalence of cardiovascular diseases. On the other hand, a deleterious effect of leptin on mitochondrial performance was described, which was also associated with the evolution of cardiac hypertrophy to heart failure. The goal of our study was to analyze the effect of the exposure of rat hearts to a high concentration of leptin on cardiac and mitochondrial function. METHODS: Rat hearts were perfused continuously with or without 3.1 nM leptin for 1, 2, 3, or 4 hours. Homogenates and mitochondria were prepared by centrifugation and analyzed for cardiac actin, STAT3, and pSTAT3 by Western blotting, as well as for mitochondrial oxidative phosphorylation, membrane potential, swelling, calcium transport, and content of oxidized lipids. RESULTS: In our results, leptin induced an increased rate-pressure product as a result of increased heart rate and contraction force, as well oxidative stress. In addition, mitochondrial dysfunction expressed as a loss of membrane potential, decreased ability for calcium transport and retention, faster swelling, and less respiratory control was observed. CONCLUSIONS: Our results support the role of leptin as a deleterious factor for cardiac function and indicates that mitochondrial dysfunction could be a trigger for cardiac hypertrophy and failure.
RESUMO
Oophorectomy in adult rats affected cardiac mitochondrial function. Progression of mitochondrial alterations was assessed at one, two and three months after surgery: at one month, very slight changes were observed, which increased at two and three months. Gradual effects included decrease in the rates of oxygen consumption and in respiratory uncoupling in the presence of complex I substrates, as well as compromised Ca2+ buffering ability. Malondialdehyde concentration increased, whereas the ROS-detoxifying enzyme Mn2+ superoxide dismutase (MnSOD) and aconitase lost activity. In the mitochondrial respiratory chain, the concentration and activity of complex I and complex IV decreased. Among other mitochondrial enzymes and transporters, adenine nucleotide carrier and glutaminase decreased. 2-Oxoglutarate dehydrogenase and pyruvate dehydrogenase also decreased. Data strongly suggest that in the female rat heart, estrogen depletion leads to progressive, severe mitochondrial dysfunction.
Assuntos
Mitocôndrias Cardíacas/metabolismo , Ovariectomia , Fosforilação Oxidativa , Consumo de Oxigênio/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Aconitato Hidratase/metabolismo , Animais , Feminino , Malondialdeído/metabolismo , Ratos , Superóxido Dismutase/metabolismoRESUMO
We investigated the effect of restraint on the release of dopamine, GABA and glutamate in the medial prefrontal cortex (mPFC) of lactating compared with virgin Wistar female rats; besides the expression of D1, neuropeptide Y Y2, GABA receptors and corticotropin-releasing factor (CRF). Results from microdialysis experiments showed that basal dopamine and GABA, but not glutamate, concentrations were higher in lactating rats. In virgin animals, immobilization caused significant increase in dopamine, whereas GABA was unchanged and glutamate reduced. In lactating animals, restrain significantly decreased dopamine concentrations and, in contrast to virgin animals, GABA and glutamate concentrations increased. We found a higher expression of CRF, as well as the D1 and neuropeptide Y Y2 receptors in the left mPFC of virgin stressed rats; also, only stressed lactating animals showed a significant increase in immunopositive cells to GABA in the left cingulate cortex; meanwhile, a significant decrease was measured in virgin rats after stress in the left prelimbic region. The increased inhibition of the mPFC dopamine cells during stress and the down-regulated expression of the neuropeptide Y Y2 receptor may explain the lower CRF and hyporesponse to stress measured in lactating animals. Interestingly, participation of mPFC in stress regulation seems to be lateralized.
Assuntos
Dopamina/metabolismo , Lactação/metabolismo , Córtex Pré-Frontal/metabolismo , Estresse Psicológico/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Hormônio Liberador da Corticotropina/metabolismo , Regulação para Baixo/fisiologia , Feminino , Ácido Glutâmico/metabolismo , Sistema Límbico/metabolismo , Microdiálise , Ratos , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Neuropeptídeo Y/metabolismoRESUMO
Bax, a pro-apoptotic member of the Bcl-2 family of proteins has the ability to form transmembrane pores large enough to allow cytochrome c (Cyt c) release, as well as to activate the mitochondrial permeability transition pore (mPTP); however, no differential study has been conducted to clarify which one of these mechanisms predominates over the other in the same system. In the present study, we treated isolated mitochondria from MCF7 cells with recombinant protein Bax and tested the efficacy of the mPTP inhibitor cyclosporin A (CsA) and of the Bax channel blocker (Bcb) to inhibit cytochrome c release. We also, induced apoptosis in MCF7 cell cultures with TNF-α plus cycloheximide to determine the effect of such compounds in apoptosis induction via mPTP or Bax oligomerization. Cytochrome c release was totally prevented by CsA and partially by Bcb when apoptosis was induced with recombinant Bax in isolated mitochondria from MCF7 cells. CsA increased the number of living cells in cell culture, as compared with the effect of Bax channel blocker. These results indicate that mPTP activation is the predominant pathway for Bax-induced cytochrome c release from MCF7 mitochondria and for apoptosis induction in the whole cell.
Assuntos
Citocromos c/metabolismo , Mitocôndrias/metabolismo , Proteína X Associada a bcl-2/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Cicloeximida/farmacologia , Ciclosporina/farmacologia , Humanos , Células MCF-7 , Mitocôndrias/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Proteína X Associada a bcl-2/antagonistas & inibidores , Proteína X Associada a bcl-2/farmacologiaRESUMO
In this work we studied the influence of sex hormones on heart and mitochondrial functions, from adult castrated female and male, and intact rats. Castration was performed at their third week of life and on the fourth month animals were subjected to heart ischemia and reperfusion. Electrocardiogram and blood pressure recordings were made, cytokines levels were measured, histopathological studies were performed and thiobarbituric acid reactive species were determined. At the mitochondrial level respiratory control, transmembranal potential and calcium management were determined; Western blot of some mitochondrial components was also performed. Alterations in cardiac function were worst in intact males and castrated females as compared with those found in intact females and castrated males, cytokine levels were modulated also by hormonal status. Regarding mitochondria, in those obtained from hearts from castrated females without ischemia-reperfusion, all evaluated parameters were similar to those observed in mitochondria after ischemia-reperfusion. The results show hormonal influences on the heart at functional and mitochondrial levels.