The Effects of Palmitic Acid on Nitric Oxide Production by Rat Skeletal Muscle: Mechanism via Superoxide and iNOS Activation

Background: Increased plasma concentrations of free fatty acids (FFA) can lead to insulin resistance in skeletal muscle, impaired effects on mitochondrial function, including uncoupling of oxidative phosphorylation and decrease of endogenous antioxidant defenses. Nitric oxide (NO) is a highly diffusible gas that presents a half-life of 5-10 seconds and is involved in several physiological and pathological conditions. The effects of palmitic acid on nitric oxide (NO) production by rat skeletal muscle cells and the possible mechanism involved were investigated. Methods: Primary cultured rat skeletal muscle cells were treated with palmitic acid and NO production was assessed by nitrite measurement (Griess method) and 4,5-diaminofluorescein diacetate (DAF-2-DA) assay. Nuclear factor-kappa B (NF-kappa B) activation was evaluated by electrophoretic mobility shift assay and iNOS protein content by western blotting. Results: Palmitic acid treatment increased nitric oxide production. This effect was abolished by treatment with NOS inhibitors, L-nitro-arginine (LNA) and L-nitro-arginine methyl esther (L-NAME). NF-kappa B activation and iNOS content were increased due to palmitic acid treatment. The participation of superoxide on nitric oxide production was investigated by incubating the cells with DAF-2-DA in the presence or absence of palmitic acid, a superoxide generator system (X-XO), a mixture of NOS inhibitors and SOD-PEG (superoxide dismutase linked to polyethylene glycol). Palmitic acid and X-XO system increased NO production and this effect was abolished when cells were treated with NOS inhibitors and also with SOD-PEG. Conclusions: In summary, palmitic acid stimulates NO production in cultured skeletal muscle cells through production of superoxide, nuclear factor-kappa B activation and increase of iNOS protein content. Copyright (C) 2012 S. Karger AG, BaselFAPESPFAPESPCNPqCNPqCAPESCAPE

Leucine-rich diet induces a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, reducing glucose consumption and metastasis in Walker-256 tumour-bearing rats

Leucine can stimulate protein synthesis in skeletal muscle, and recent studies have shown an increase in leucine-related mitochondria! biogenesis and oxidative phosphorylation capacity in muscle cells. However, leucine-related effects in tumour tissues are still poorly understood. Thus, we described the effects of leucine in both in vivo and in vitro models of a Walker-256 tumour. Tumour-bearing Wistar rats were randomly distributed into a control group (W; normoprotein diet) and leucine group (LW; leucine-rich diet [normoprotein +3% leucine]). After 20 days of tumour evolution, the animals underwent (18)-fludeoxyglucose positron emission computed tomography (F-18-FDG PET-CT) imaging, and after euthanasia, fresh tumour biopsy samples were taken for oxygen consumption rate measurements (Oroboros Oxygraph), electron microscopy analysis and RNA and protein extraction. Our main results from the LW group showed no tumour size change, lower tumour glucose (F-18-FDG) uptake, and reduced metastatic sites. Furthermore, leucine stimulated a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, higher mRNA and protein expression of oxidative phosphorylation components, and enhanced mitochondria! density/area even though the leucine-treated tumour had a higher number of apoptotic nuclei with increased oxidative stress. In summary, a leucine-rich diet directed Walker-256 tumour metabolism to a less glycolytic phenotype profile in which these metabolic alterations were associated with a decrease in tumour aggressiveness and reduction in the number of metastatic sites in rats fed a diet supplemented with this branched-chain amino acid.9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informação302863/2013-3; 302425/2016-92012/06955-0; 2014/13334-7; 2015/21890-0; 2017/02739-

Hydrogen peroxide production regulates the mitochondrial function in insulin resistant muscle cells: Effect of catalase overexpression

AbstractThe mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500μM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with β-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and β-oxidation of fatty acids

Optical Properties And Antiangiogenic Activity Of A Chalcone Derivate

Chalcones and their derivatives exhibit numerous pharmacological activities such as antibacterial, antifungal, cytotoxic, antinociceptive and anti-inflammatory. Recently, they have been assessed aiming for novel application in nonlinear optics and in the treatment of immune diseases and cancers. In this study, we investigate the optical properties of synthetic chalcona 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one (CAB7β) and its antiangiogenic potential using the chorioallantoic membrane (CAM) with the S180 sarcoma cell line. Experimental and theoretical results show intense absorption in the UVA-UVC region, which is associated with a π → π* transition with intramolecular charge transfer from the trimethyl-cyclohexen-1-yl ring to the chlorophenyl ring. Quantum chemical calculations of the first hyperpolarizability, accounting for both solvent and frequency dispersion effects, are in very good concordance with hyper-Rayleigh scattering measurements. In addition, two-photon absorption allowed band centered at 650 nm was observed. Concerning antiangiogenic activity, CAB7β causes a significant reduction in the total number, junctions, length and caliber of blood vessels stimulated by S180 cells reducing the presence of blood vessels, inflammatory cells and others elements related to angiogenic process. It is found that CAB7β is a versatile compound and a promising candidate for linear and nonlinear optical applications, in therapy against sarcoma and phototherapy

Efeito de emulsificantes sobre processo de extrusão e na análise sensorial de alimento seco para cães

Objetivou-se com essa pesquisa avaliar os efeitos de aditivos emulsificantes em características de processo e textura dos kibbles na indústria pet food. Para cada tratamento, foram realizadas quatro batidas (4 repetições/tratamento) e coletadas quatro amostras no tempo. Dois emulsificantes comerciais, adicionados on top, foram utilizados em um alimento seco extrusado, indicado para cães adultos, formando 3 tratamentos ((CON; Controle), (EMUA; CON + 0,06% emulsificante A), (EMUB; CON + 0,06% emulsificante B)). Foi utilizada dieta comercial econômica para cães adultos. Os alimentos foram extrusados em uma extrusora de rosca simples, com capacidade de processamento de 6.000 kg/h, sendo que o mesmo conjunto de equipamentos, condições de mistura, secagem e revestimento foram utilizados para todos os tratamentos. O emulsificante A possui em sua composição mono-diglicerídeo parcialmente saturado, estearoil lactato de sódio e mono éster de ácido tartárico di-acetilado, enquanto o emulsificante B possui em sua composição mono e diglicerídeos de ácidos graxos, ésteres de monoglicerídeos com ácido diacetiltartárico e estearoil lactato de sódio.  Foi realizada uma análise de correlação canônica para os dados de correlação de processos e características de textura de kibble. O teste multivariado lambda Wilks foi usado para avaliar a significância das raízes canônicas juntas. Observou-se que a função canônica 1 mostrou-se significante. Percebeu-se que houve controle no processo, devido ao agrupamento dos tratamentos. A utilização de emulsificantes influenciou a característica de dureza dos kibbles, com menor resistência de EMUA (54,731 ±1,124), quando comparado a EMUB (121,898± 5,158). O tratamento EMUB obteve valores de amperagem, potência e consumo de energia inferiores aos demais tratamentos (P<0,05). Houve uma redução no valor da Amperagem, em relação ao tratamento CON de 1,43% e 3,15%, respectivamente, para os tratamentos EMUA e EMUB. Conclui-se que EMUB contribui mais significativamente para obtenção de características de textura e para o processo de extrusão

Saco de plástico dual

DepositadaA presente invenção se refere a um saco de plástico com dois compartimentos. Mais especificamente, se refere a um saco de plástico primeiramente intencionado para jogar lixo reciclável de dois tipos, por exemplo, um compartimento para pel/papelão/embalagens e um compartimento para material orgânico

Changes in PGC-1α-Dependent Mitochondrial Biogenesis Are Associated with Inflexible Hepatic Energy Metabolism in the Offspring Born to Dexamethasone-Treated Mothers

In the present study we investigated the participation of hepatic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) in the metabolic programming of newborn rats exposed in utero to dexamethasone (DEX). On the 21st day of life, fasted offspring born to DEX-treated mothers displayed increased conversion of pyruvate into glucose with simultaneous upregulation of PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose-6-phosphatase). Increased oxidative phosphorylation, higher ATP/ADP ratio and mitochondrial biogenesis and lower pyruvate levels were also found in the progeny of DEX-treated mothers. On the other hand, the 21-day-old progeny of DEX-treated mothers had increased hepatic triglycerides (TAG) and lower CPT-1 activity when subjected to short-term fasting. At the mechanistic level, rats exposed in utero to DEX exhibited increased hepatic PGC-1α protein content with lower miR-29a-c expression. Increased PGC-1α content was concurrent with increased association to HNF-4α and NRF1 and reduced PPARα expression. The data presented herein reveal that changes in the transcription machinery in neonatal liver of rats born to DEX-treated mothers leads to an inflexible metabolic response to fasting. Such programming is hallmarked by increased oxidative phosphorylation of pyruvate with impaired FFA oxidation and hepatic TAG accumulation.</jats:p

Dispositivo filtrador de água

DepositadaO presente modelo de utilidade se refere a um dispositivo filtrador de água, o qual compreende uma unidade em forma de um poste a ser colocado particularmente em lugares ao ar livre, dito dispositivo compreendendo um filtro, uma cisterna e pelo menos uma bica. O dispositivo é suprido com água da rede de água da cidade. No topo do poste pode ser providenciado uma luminária energizada com energia solar. Desta maneira é oferecida água potável para o cidadão, sem necessidade de garrafas de plástico

Dispositivo de mitigação de efeitos de alagamento utilizando polímeros superabsorventes

DepositadaA presente Patente de Invenção tem por objetivo um dispositivo voltado para absorver água em seu interior e evitar alagamentos em diversas situações e variações construtivas. O presente dispositivo pode ser produzido em pelo menos três variações construtivas, segundo três modelos, um dos modelos é composto de uma estrutura externa, provida de recipientes em forma de rebaixos preenchidos interiormente com fios retilíneos de SAP distribuídos de forma aleatória e não regular e recoberta por uma camada de material poroso e uma camada de tapete de grama ou similar; outro modelo é composto de um envoltório semipermeável com material polimérico, onde será depositada uma camada de SAP revestida por uma camada de material poroso como cortiça, areia, serragem ou brita, sendo sobre esta depositado o tapete comercial de grama ou plantio da própria grama a partir de sementes; outro modelo é composto uma camada de SAP depositada em recipiente adequado adjacente, possuindo este uma cobertura composta impermeável com suficiente resistência mecânica, sendo esta fixada à estrutura de um recipiente por meio de uma dobradiça ou similar