A new model of short acceleration-based training improves exercise performance in old mice.

In order to identify a more appealing exercise strategy for the elderly, we studied a mouse model to determine whether a less time-consuming training program would improve exercise performance, enzyme activities, mitochondrial respiration, and metabolomic parameters. We compared the effects of short-session (acceleration-based) training with those of long-session endurance training in 23-month-old mice. The short-session training consisted of five acceleration-based treadmill running sessions over 2 weeks (the acceleration group), whereas the endurance training consisted of five-one-hour treadmill sessions per week for 4 weeks (the endurance group). A control group of mice was also studied. In the acceleration group, the post-training maximum running speed and time to exhaustion were significantly improved, relative to pretraining values (+8% for speed, P<.05; +10% for time to exhaustion, P<.01). The post-training maximum running speed was higher in the acceleration group than in the endurance group (by 23%; P<.001) and in the control group (by 15%; P<.05). In skeletal muscle samples, the enzymatic activities of citrate synthase, lactate dehydrogenase, and creatine kinase were significantly higher in the acceleration group than in the endurance group. Furthermore, mitochondrial respiratory activity in the gastrocnemius was higher in the acceleration group than in the control group. A metabolomic urine analysis revealed a higher mean taurine concentration and a lower mean branched amino acid concentration in the acceleration group. In old mice, acceleration-based training appears to be an efficient way of increasing performance by improving both aerobic and anaerobic metabolism, and possibly by enhancing antioxidant defenses and maintaining muscle protein balance.

Biomarker exposure of phenolic compounds from grumixama (Eugenia brasiliensis Lam. ) in healthy human model: Metabolomic approach / Identificação de biomarcadores de exposição de compostos fenólicos degrumixama (Eugenia brasiliensis Lam. ): Abordagem metabolômica

The fruits and vegetables intake has been associated to the reduction of chronic non-communicable disease incidence, such as cancer, metabolic syndrome and cardiovascular diseases. The biological activities attribute to them has been related mainly to the phenolic compounds, such as flavonoids and ellagitannins, presents in their composition. However, the bioavailability and influence of these compounds under human metabolism still unclear. Thus, the objective of the present study was investigate changes in human metaboloma as a result of the acute intake of the polyphenol-rich source from purple grumixama juice (Eugenia brasiliensis Lam.), searching to identify possible sites of metabolic regulation. In this way, purple and yellow grumixama varieties were characterized to polyphenol profile, and a single dose of the purple grumixama juice was administered to healthy human. The purple grumixama showed be a good source of anthocyanins and ellagitannins, mainly cyanidin 3-O-glucoside and strictinin, respectively. In the clinical trial, 15 healthy subjects intake a single dose of purple grumixama juice (10 ml of juice/kg of body mass). Plasma and urine samples were collected, before and after intake (over 24 h), and analyzed by GC-MS and LC-MS. The exogenous metabolites excreted and identified in urine samples by LC-MS were identified as urolithins and phenolic acids, gut microbiota catabolites of ellagitannins and anthocyanins, respectively. Four urolithins were detected beginning excretion 4 h after juice intake, increasing over 24 h. Furthermore, four phenolic acids were identified, being the hippuric acid the majority of them. 114 metabolites were identified to urine collection points before and after intake (1-2 h and 2-4 h) by CG-MS, being 17 amino acids, 7 other classes, 47 organic acids and 43 unknown compounds. A OPLS-DA discriminated the metabolites changed by the grumixama juice intake. The pathway analysis showed that juice intake influenced mainly three metabolic pathways: glyoxylate and dicarboxylate metabolism (up-regulated), beta-alanine metabolism (down-regulated), and phenylalanine metabolism (up-regulated), being these pathways related to energetic metabolism. Furthermore, the purple and yellow grumixama fruits extracts were evaluated in animal model of obesity and insulin resistance (C57BL/6J mice) induced by high fatty and high sugar diet. The treatment, during 8 weeks, promoted lipid metabolism modulation. As conclusions, purple grumixama showed to be a good source of anthocyanins and ellagitannins, and the interaction among the metabolites from fruits and endogenous metabolites can be related to changes in energetic metabolism and amino acid metabolism. However, more studies are necessary to elucidate and validate these hypotheses

O consumo de frutas e verduras na dieta está associado à redução da incidência de doenças crônicas não transmissíveis entre eles câncer, síndrome metabólica e doenças cardiovasculares. A atividade biológica atribuída à ingestão desses alimentos é relacionada principalmente à presença de compostos bioativos, entre eles os compostos fenólicos, tais como flavonoides e elagitaninos. Contudo, a biodisponibilidade e a influência destes compostos no metabolismo humano não estão estabelecidas. Assim, o objetivo geral do presente estudo foi investigar as alterações no metaboloma humano decorrente da ingestão de uma fonte rica em compostos fenólicos, o suco da grumixama roxa (Eugenia brasiliensis Lam.), buscando identificar possíveis pontos de regulação do metabolismo. Para isto, a grumixama, variedades amarela e roxa, foram caracterizadas quanto ao seu perfil de compostos fenólicos e administradas na forma de suco, em dose única, a voluntários saudáveis. A grumixama roxa se mostrou rica em antocianinas e elagitaninos, principalmente cianidina 3-O-glicosídeo e a strictinina, respectivamente. Para o ensaio clínico, 15 voluntários saudáveis consumiram, em dose única, suco de grumixama roxa (10 ml de suco/kg de peso corporal). Amostras de plasma e urina foram coletadas em diferentes tempos durante 24 h após ingestão e analisados por CG-MS e LC-ESI-MS/MS. Os metabólitos exógenos excretados na urina foram identificados como urolitinas e ácidos fenólicos, derivados da degradação, principalmente, pela microbiota dos elagitaninos e das antocianinas, respectivamente. Quatro urolitinas (A, B, C e D) foram encontradas na urina, principalmente como metabólitos de fase II, detectados a partir de 4 h após a ingestão do suco com aumento na concentração observado até 24h. Além disso, quatro ácidos fenólicos foram identificados, destes o ácido hipúrico como majoritário. 114 metabólitos, entre eles, 17 aminoácidos, 47 ácidos orgânicos, 7 outras classes de compostos e 43 compostos desconhecidos foram identificados por CG-MS, para os tempos de coleta de urina antes da ingestão de suco de grumixama (T0) e para os períodos de 1-2 h e 2-4 h após a ingestão. A OPLS-DA foi utilizada para descriminar os metabólitos alterados pela ingestão de suco de grumixama. A análise das vias metabólicas mostrou que a ingestão do suco de grumixama influenciou principalmente em três vias metabólicas: metabolismo do glioxilato e dicarboxilato (up-regulated), da beta-alanina (down-regulated) e da fenilalanina (up-regulated), sendo essas direcionadas ao metabolismo energético. Além disso, os extratos de grumixama roxa e amarela também foram testados em modelo animal (camundongo C57BL/6J) de obesidade e resistência à insulina induzido por uma dieta rica em lipídeos e açúcares. O tratamento com os extratos, concomitante à dieta e durante 8 semanas, promoveu modulação significativa do metabolismo lipídico. Como conclusões, a grumixama roxa mostrou ser uma boa fonte de antocianinas e elagitaninos, e a interação entre metabólitos oriundos da ingestão do fruto e dos metabólitos endógenos podem estar relacionados com alterações nos metabolismos de aminoácidos e energético. No entanto, mais estudos são necessários para elucidar e validar as hipóteses geradas