Association between diet and polymorphisms in individuals with statin-controlled dyslipidaemia grouped according to oxidative stress biomarkers

The objective of this study was to investigate whether differences in diet and in single-nucleotide polymorphisms (SNPs) found in paraoxonase-1 (PON-1), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) genes, are associated with oxidative stress biomarkers and consequently with susceptibility of low-density cholesterol (LDL) to oxidation. A multivariate approach was applied to a group of 55 patients according to three biomarkers: plasma antioxidant activity, malondialdehyde and oxidized LDL (oxLDL) concentrations. Individuals classified in Cluster III showed the worst prognoses in terms of antioxidant activity and oxidative status. Individuals classified in Cluster I presented the lowest oxidative status, while individuals grouped in Cluster II presented the highest levels of antioxidant activity. No difference in nutrient intake was observed among the clusters. Significantly higher gamma- and delta-tocopherol concentrations were observed in those individuals with the highest levels of antioxidant activity. No single linear regression was statistically significant, suggesting that mutant alleles of the SNPs selected did not contribute to the differences observed in oxidative stress response. Although not statistically significant, the p value of the APO E coefficient for oxLDL response was 0.096, indicating that patients who carry the TT allele of the APO E gene tend to present lower plasma oxLDL concentrations. Therefore, the differences in oxidative stress levels observed in this study could not be attributed to diet or to the variant alleles of PON-1, CETP, HMGCR or APO E. This data supports the influence of gamma-tocopherol and delta-tocopherol on antioxidant activity, and highlights the need for further studies investigating APO E alleles and LDL oxidation.O objetivo deste estudo foi investigar se diferenças na dieta e em polimorfismos de nucleotídeos únicos (SNPs) encontrados no gene da paraoxonase 1 (PON-1), da 3-hidroxi-3-metilglutaril-coenzima A reductase (HMGCR), da proteína de transferência de ésteres de colesterol (CETP) e da apolipoproteina E (APOE) estariam associadas com biomarcadores do estresse oxidativo e, consequentemente, com a suscetibilidade da LDL à oxidação. Técnicas da estatística multivariada foram aplicadas a um grupo de 55 pacientes usando 3 biomarcadores: atividade antioxidante plasmática, concentrações de malondialdeído e LDL oxidada. Indivíduos classificados no cluster III apresentaram um prognóstico negativo em termos de atividade antioxidante e estado oxidativo. Os indivíduos agrupados no cluster I apresentaram o mais baixo nível de estado oxidativo, enquanto que indivíduos no cluster II apresentaram os mais altos níveis de atividade antioxidante. Nenhuma diferença na ingestão de nutrientes foi observada entre os clusters. Concentrações estatísticamente mais altas de γ- e δ-tocoferol foram observadas em indivíduos com mais altos níveis de atividade antioxidante. A regressão linear aplicada não foi estaticamente significativa, sugerindo que os alelos mutantes dos SNPs selecionados não contribuíram para as diferenças nos níveis de estresse oxidativo. Embora não tenha sido estatisticamente significativa, o valor da probabilidade associado ao coeficiente da relação entre ApoE e oxLDL foi de 0,096, indicando que pacientes que carregam o alelo TT da ApoE tendem a apresentar menores concentrações plasmáticas de LDL oxidada. Portanto, as diferenças no estresse oxidativo observadas em nosso estudo não puderam ser atribuídas à dieta e alelos variantes de PON-1, CETP, HMGCR ou ApoE. Nossos dados suportam a influência γ- tocoferol e δ-tocoferol na atividade antioxidante e reforçam a necessidade de mais pesquisas que investiguem a relação entre alelos da Apo E e a oxidação da LDL.FAPESP [07/01476-8, 08/00482-7, 08/10826-5

Effect of Echium oil compared with marine oils on lipid profile and inhibition of hepatic steatosis in LDLr knockout mice

Abstract\ud \ud \ud \ud Background\ud \ud In an effort to identify new alternatives for long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) supplementation, the effect of three sources of omega 3 fatty acids (algae, fish and Echium oils) on lipid profile and inflammation biomarkers was evaluated in LDL receptor knockout mice.\ud \ud \ud \ud Methods\ud \ud The animals received a high fat diet and were supplemented by gavage with an emulsion containing water (CON), docosahexaenoic acid (DHA, 42.89%) from algae oil (ALG), eicosapentaenoic acid (EPA, 19.97%) plus DHA (11.51%) from fish oil (FIS), and alpha-linolenic acid (ALA, 26.75%) plus stearidonic acid (SDA, 11.13%) from Echium oil (ECH) for 4 weeks.\ud \ud \ud \ud Results\ud \ud Animals supplemented with Echium oil presented lower cholesterol total and triacylglycerol concentrations than control group (CON) and lower VLDL than all of the other groups, constituting the best lipoprotein profile observed in our study. Moreover, the Echium oil attenuated the hepatic steatosis caused by the high fat diet. However, in contrast to the marine oils, Echium oil did not affect the levels of transcription factors involved in lipid metabolism, such as Peroxisome Proliferator Activated Receptor α (PPAR α) and Liver X Receptor α (LXR α), suggesting that it exerts its beneficial effects by a mechanism other than those observed to EPA and DHA. Echium oil also reduced N-6/N-3 FA ratio in hepatic tissue, which can have been responsible for the attenuation of steatosis hepatic observed in ECH group. None of the supplemented oils reduced the inflammation biomarkers.\ud \ud \ud \ud Conclusion\ud \ud Our results suggest that Echium oil represents an alternative as natural ingredient to be applied in functional foods to reduce cardiovascular disease risk factors.The authors thank to FAPESP (09/15649-7; 10/12042-1, 10/08225-3) for the financial support

Influence of physical exercise on chemical lean body mass composition of rats submitted to food restriction

A combinação de uma dieta para redução de peso corporal com exercício físico (EF) pode resultar em menor diminuição de massa magra (MM), quando comparada ao uso da dieta como única estratégia de emagrecimento. Contudo, pouco se conhece sobre a influência dessa combinação na composição química da MM. Diante disso, o presente estudo teve como objetivo verificar o efeito do EF na composição química da MM de ratos submetidos à restrição alimentar (RA). Trinta e seis ratos Wistar (315 ± 15 g) foram divididos em 6 grupos: sedentário, com dieta ad libitum (S); treinado, com dieta ad libitum (T); S, com RA de 25% (RA25%); S, com RA de 50% (RA50%); T, com RA de 25% (T + RA25%) e T, com RA de 50% (T + RA50%). O experimento durou seis semanas e o treinamento utilizado foi a natação, com sobrecarga de 5% do peso corporal, cinco sessões/semana de 60 minutos cada. Foram avaliadas a composição química da carcaça e a concentração de glicogênio e de proteína no músculo gastrocnêmio dos animais. O percentual de proteína da carcaça e a concentração de proteína do músculo gastrocnêmio dos animais dos grupos T + RA25% e T + RA50% foram menores (pThe combination of a diet for body weight reduction with physical exercise (PE) can result in a smaller decrease in lean mass ((LM) compared to the use of a diet as the single strategy for weight loss. However, little is known about the influence of this combination on LM composition. On this basis, the objective of the present study was to determine the effect of PE on LM composition in rats submitted to food restriction (FR). Thirty-six Wistar rats (315 ± 15 g) were divided into the following 6 equal groups: sedentary with an ad libitum diet (S); trained, with an ad libitum diet (T); S, with 25% FR (FR25%); S, with 50% FR (FR50%); T, with FR25% (T + FR25%), and T with FR50% (T + FR50%). The experiment lasted six weeks and the training used was swimming with an overload of 5% of body weight, five sessions/week of 60 minutes each. The chemical composition of the carcass and the concentration of glycogen and protein in the gastrocnemius muscle of the animals were determined. The percentage of protein in the carcass and the concentration of protein in the gastrocnemius muscle were lower (

Effects of Diets Supplemented with Branched-Chain Amino Acids on the Performance and Fatigue Mechanisms of Rats Submitted to Prolonged Physical Exercise

This study aimed to determine the effects of diets chronically supplemented with branched-chain amino acids (BCAA) on the fatigue mechanisms of trained rats. Thirty-six adult Wistar rats were trained for six weeks. The training protocol consisted of bouts of swimming exercise (one hour a day, five times a week, for six weeks). The animals received a control diet (C) (n = 12), a diet supplemented with 3.57% BCAA (S1) (n = 12), or a diet supplemented with 4.76% BCAA (S2) (n = 12). On the last day of the training protocol, half the animals in each group were sacrificed after one hour of swimming (1H), and the other half after a swimming exhaustion test (EX). Swimming time until exhaustion was increased by 37% in group S1 and reduced by 43% in group S2 compared to group C. Results indicate that the S1 diet had a beneficial effect on performance by sparing glycogen in the soleus muscle (p < 0.05) and by inducing a lower concentration of plasma ammonia, whereas the S2 diet had a negative effect on performance due to hyperammonemia (p < 0.05). The hypothalamic concentration of serotonin was not significantly different between the 1H and EX conditions. In conclusion, chronic BCAA supplementation led to increased performance in rats subjected to a swimming test to exhaustion. However, this is a dose-dependent effect, since chronic ingestion of elevated quantities of BCAA led to a reduction in performance.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Inhibition of connexin hemichannels alleviates non-alcoholic steatohepatitis in mice

While gap junctions mediate intercellular communication and support liver homeostasis, connexin hemichannels are preferentially opened by pathological stimuli, including inflammation and oxidative stress. The latter are essential features of non-alcoholic steatohepatitis. In this study, it was investigated whether connexin32 and connexin43 hemichannels play a role in non-alcoholic steatohepatitis. Mice were fed a choline-deficient high-fat diet or normal diet for 8 weeks. Thereafter, TAT-Gap24 or TAT-Gap19, specific inhibitors of hemichannels composed of connexin32 and connexin43, respectively, were administered for 2 weeks. Subsequently, histopathological examination was carried out and various indicators of inflammation, liver damage and oxidative stress were tested. In addition, whole transcriptome microarray analysis of liver tissue was performed. Channel specificity of TAT-Gap24 and TAT-Gap19 was examined in vitro by fluorescence recovery after photobleaching analysis and measurement of extracellular release of adenosine triphosphate. TAT-Gap24 and TAT-Gap19 were shown to be hemichannel-specific in cultured primary hepatocytes. Diet-fed animals treated with TAT-Gap24 or TAT-Gap19 displayed decreased amounts of liver lipids and inflammatory markers, and augmented levels of superoxide dismutase, which was supported by the microarray results. These findings show the involvement of connexin32 and connexin43 hemichannels in non-alcoholic steatohepatitis and, simultaneously, suggest a role as potential drug targets in non-alcoholic steatohepatitis

Effect of L-glutamine and L-alanyl-L-glutamine supplementation on the response to delayed-type hypersensitivity test (DTH) in rats submitted to intense training

O treinamento intenso e o exercício exaustivo podem ocasionar imunossupressão em atletas por meio da diminuição da concentração plasmática de glutamina. O presente estudo verificou inicialmente o efeito da suplementação com L-glutamina e L-alanilL-glutamina sobre a resposta ao teste de hipersensibilidade do tipo tardio (HTT) em ratos submetidos ao treinamento intenso em natação durante seis semanas. Posteriormente, foi avaliado o efeito dessas intervenções nutricionais sobre a contagem total e porcentual de leucócitos e concentração sérica de anticorpos IgG anti-albumina de soro bovino, em animais submetidos ao teste de exaustão e recuperados durante o período de 3 horas. Não houve efeito do treinamento e da suplementação sobre a resposta ao teste de HTT. Animais suplementados apresentaram maior concentração de glutamina no plasma (PIntense training and exhaustive exercise may cause immunesupression in athletes by reducing plasma glutamine concentration. Initially, this study verified the effect of L-glutamine and L-alanyl-L-glutamine supplementation on the response to delayed-type hypersensitivity test (DTH) in rats submitted to intense swimming training for six weeks. Later on, we assessed the effect of these nutritional interventions on total and differential white blood cell counts and on concentration of anti-bovine serum albumin IgG antibodies, in animals submitted to exhaustion test and a three-hour recovery period. There was no effect of training and supplementation on the response to DTH. Supplemented animals presented greatest plasma glutamine concentration (

Effects of Dietary Glutamine Supplementation on the Body Composition and Protein Status of Early-Weaned Mice Inoculated with Mycobacterium bovis Bacillus Calmette-Guerin

Glutamine, one of the most abundant amino acids found in maternal milk, favors protein anabolism. Early-weaned babies are deprived of this source of glutamine, in a period during which endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress, mainly during infections. The objective of this study was to verify the effects of dietary glutamine supplementation on the body composition and visceral protein status of early-weaned mice inoculated with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Mice were weaned early on their 14th day of life and seperated into two groups, one of which was fed a glutamine-free diet (n = 16) and the other a glutamine-supplemented diet (40 g/kg diet) (n = 16). At 21 days of age, some mice were intraperitoneally injected with BCG. Euthanasia was performed at the 28th day of age. BCG inoculation significantly reduced body weight (P < 0.001), lean mass (P = 0.002), water (P = 0.006), protein (P = 0.007) and lipid content (P = 0.001) in the carcass. Dietary glutamine supplementation resulted in a significant increase in serum IGF-1 (P = 0.019) and albumin (P = 0.025) concentration, muscle protein concentration (P = 0.035) and lipid content (P = 0.002) in the carcass. In conclusion, dietary glutamine supplementation had a positive influence on visceral protein status but did not affect body composition in early-weaned mice inoculated with BCG

Protein mixtures and their nutritional properties optimized by response surface methodology

Gelatina Hidrolisada (GH), Glúten de Trigo (GT) e Isolado Protéico de Soja (IPS) foram misturados em diferentes proporções com o objetivo de substituir proteínas lácteas em uma formulação alimentícia utilizada em programas institucionais de alimentação escolar, buscando-se uma redução de custos sem alterações significativas das propriedades nutricionais e sensoriais do produto final. A qualidade nutricional das misturas foi avaliada de acordo com os métodos \"Escore Químico corrigido pela Digestibilidade PDCAAS\" e \"Razão de Eficiência Protéica - NPR\". As misturas, aplicadas àformulação de uma bebida láctea, foram avaliadas sensorialmente através do método de \"Diferença Escalar do Controle\". Os resultados obtidos experimentalmente pelo delineamento simplex-centróide foram utilizados para modelar equações canônicas de Scheffé que pudessem descrever o efeito da proporção de cada componente na qualidade final. Todos os resultados foram correlacionados através de análise multivariada e representados na forma de Análise de Componente Principal (ACP). Uma \"solução de compromisso\" contendo 25% de GH, 15% GT e 60% de IPS foi selecionada na otimização conjunta das respostas nutricional, sensorial e econômica, resultando na redução média de 6% do custo do produto final sem alteração significativa de qualidade (p < 0,01). Estes resultados revelaram a eficiência da utilização de técnicas estatísticas multivariadas na otimização simultânea e na visualização das interações que ocorrem em processos complexos como sistemas biológicos.Hidrolizated Gelatin (HG), Wheat Gluten (WG) and Soybean Protein Isolate (SPI) were mixed at different proportions in order to partially replace milk proteins in food formulation utilized in Food Programs to reduce its cost without significant decrease in its nutritional and sensorial properties. The nutritional quality of the mixtures was evaluated by the \"Protein DigestibilityCorrected Amino Acid Score (PDCAAS)\" and \"Net Protein Ratio (NPR)\"methods. The sensorial quality of the mixtures was evaluated by the \"Scale Difference of Control\". The results obtained experimentally by simplex design were used to elaborate Scheffé\'s canonical equations that would describe the effect of the proportion of each component on the final nutritional quality of the product. Ali the results were correlationed by Multivariate Analysis and represented by Principal Component Analysis (PCA). A \"compromise solution\" containing 25% HG, 15% WG and 60% SPI was selected as multiresponse optimization. This mixture was applicated in food formulation and submitted to the evaluations of nutrition and sensorial quality. The final product showed about 6% of cost reduction without any significant change in its quality (p< 0,01). These results demonstrated the statistics multivariate methods efficiency in simultaneous optimization and visualization of interactions which are present in complex process like biological systems