Search Results (3)

Objectives: We have previously shown that inhibition of the mTORC1 nutrient-sensing complex by rapamycin and mTORC1/mTORC2 inhibition by either Torin-2 or RapaLink-1 have differential effects on the global untargeted metabolomics in in vivo and in vitro cell culture models. Methods: In this study, we leveraged the mummichog Python algorithm to analyze the high-dimension untargeted metabolomics data to model the biochemical pathways and metabolic networks and predict their functional activity. We used pancreatic beta-cell culture (Beta TC6) and incubated the cells with either Rapalink-1, Rapamycin or the vehicle control for 24 h. Cells were harvested and flush-frozen in liquid nitrogen. Cells were extracted in ethanol, and the supernatant was collected. The untargeted metabolomics was performed using the high-resolution mass spectrometry LC-MS/MS HILIC peak detection of ESI-positive and -negative polarity modes. The data were collected using Bruker’s maXis-II ESI-Q-q-TOF coupled to Dionex Ultimate-3000 U(H)PLC system using Sequant ZIC-HILIC 150 × 2.1 mm column (Bruker, Hamburg, Germany). We compared the high-resolution untargeted precision metabolomics (LC-MS/MS) between groups using positive and negative polarity modes to capture both hydrophilic and hydrophobic metabolites. We employed the XCMS plus bioinformatics platform to link mTOR-regulated metabolites to the predicted biological pathways. Statistical significance (p < 0.001) was assessed by ANOVA and Ranked order data by Whitney-Cox followed by ad hoc unpaired t-test. Results: The cluster heatmap deconvolution and cloud plot analysis show the differential pattern of metabolites between Rapamycin and Rapalink-treated pancreatic beta cell lines. Mapping the downstream metabolites data onto predictive metabolic pathways and activity networks revealed that the top pathways affected included the pentose phosphate pathway, dopamine and ubiquinol degradation pathways in the ESI-positive polarity mode, and creatine synthesis/glycine degradation and nicotine degradation pathways in the ESI negative polarity mode. Conclusions: The high-resolution untargeted metabolomics can be leveraged as a proxy of the internal exposome yielding high-dimensional data that provide mechanistic insights into metabolic and signaling pathways, and the underlying biology. This approach will have beneficial applications of the internal exposome in determining the optimal precision nutrition pathways for personalized medicine. Full article

The aim of this work was to evaluate, by an untargeted metabolomics approach, changes of milk metabolites induced by the replacement of soybean hulls with cocoa husks in the ewes’ diet. Animals were fed with a soybean diet integrated with 50 or 100 g/d of cacao husks. Milk samples were analyzed by an ultra high performance liquid chromatograph coupled to a time of flight mass spectrometer (UHPLC-QTOF-MS) platform. Multivariate statistical analysis showed that the time of sampling profoundly affected metabolite levels, while differences between treatments were evident at the fourth week of sampling. Cocoa husks seem to induce level changes of milk metabolites implicated in the thyroid hormone metabolism and ubiquinol-10 biosynthesis. Full article

Background: Pediatric dilated cardiomyopathy (PDCM) is a life-threatening type of cardiac muscle dysfunction in children. Ubiquinone is a lipid-soluble nutrient that participates in energy synthesis. Recently, a novel hydrophilic ubiquinol supplement was developed. The purpose of this study was to assess the effect of liquid ubiquinol supplementation (10 mg/kg body weight/day) on cardiac function in children with PDCM. Methods: Ten children diagnosed with PDCM were recruited to this study and administered with liquid ubiquinol for 24 weeks. The cardiac function was measured by echocardiography. The New York Heart Association (NYHA) functional classification was used to assess symptoms of heart failure. Plasma coenzyme Q10 levels were measured during the study. Results: Ejection fraction (EF) and fractional shortening (FS) were significantly higher than the baseline values until week 16 of supplementation. Subjects who had higher plasma coenzyme Q10 concentration had significantly better EF and FS values. In addition, 30% of the subjects showed improvement in the NYHA classification after 24 weeks of supplementation. Conclusion: Liquid ubiquinol supplementation is associated with an increase the level of coenzyme Q10 to complementary improve cardiac function (particularly EF and FS) and ameliorate the symptoms of heart failure in children with PDCM. Full article