{ "METABOLOMICS WORKBENCH":{"STUDY_ID":"ST000631","ANALYSIS_ID":"AN000963","VERSION":"1","CREATED_ON":"June 25, 2017, 8:54 am"}, "PROJECT":{"PROJECT_TITLE":"Metabolomic Mechanisms of Dietary Salt Effects on Blood Pressure","PROJECT_SUMMARY":"Enhanced sensitivity of blood pressure to salt intake is observed in approximately 50% of hypertensive patients, reaching 75% in African American hypertensive patients. We recently discovered a novel role of abnormal cellular intermediary metabolism in hypertension in the Dahl salt-sensitive (SS) rat, the most commonly used polygenic, hereditary model of human salt-sensitive hypertension. We propose to test the hypothesis that blood pressure sensitivity to dietary salt intake in human is associated with metabolite changes in the urine. Leveraging the expertise and resources at the Mayo Clinic Metabolomics Resources Core, we propose to perform targeted LC/MS analysis and NMR spectra generation in urine samples obtained from a subset of subjects from the Dietary Approaches to Stop Hypertension – Sodium (DASH2) clinical trial and kidney tissue extract and urine samples from SS rats and a newly generated transgenic rat that overexpresses fumarase (SS.Fh1+). The study will be the first to systematically characterize urinary metabolite profiles associated with blood pressure response to salt in humans. The study is anticipated to generate new insight into the mechanisms (particularly renal mechanisms) underlying salt-sensitive hypertension. Findings of the proposed study could lead to an expanded clinical study as well as mechanistic studies in animal models.","INSTITUTE":"Mayo Clinic","LAST_NAME":"Liang","FIRST_NAME":"Mingyu","ADDRESS":"Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226","EMAIL":"mliang@mcw.edu","PHONE":"414-955-8539"}, "STUDY":{"STUDY_TITLE":"TCA Cycle Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine (part IV)","STUDY_SUMMARY":"We propose to analyze kidney tissue extract and urine samples from SS and SS.Fh1+ transgenic rats in addition to the analysis of urine samples from the DASH2 trial. The analysis of the rat samples will be highly valuable for several reasons. First, it will to take the findings in human subjects back to animal models and prepare us for further mechanistic studies. We hypothesize at least some of the effects of dietary salt intake on metabolite profiles in human will be recapitulated or altered in the SS rat. If this is confirmed, we will have a highly informative animal model ready for mechanistic studies in which we can investigate the functional contribution of specific metabolites to hypertension and the mechanisms involved. Second, the rat study will allow us to take advantage of a new and unique transgenic SS.Fh1+ model that we recently developed that overexpresses fumarase (Fh1) on the genetic background of the SS rat. Fumarase is a TCA cycle enzyme previously implicated in salt-induced hypertension in SS rats.","INSTITUTE":"Mayo Clinic","LAST_NAME":"Liang","FIRST_NAME":"Mingyu","ADDRESS":"Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226","EMAIL":"mliang@mcw.edu","PHONE":"414-955-8539"}, "SUBJECT":{"SUBJECT_TYPE":"Rat","SUBJECT_SPECIES":"Rattus norvegicus","TAXONOMY_ID":"10116"}, "SUBJECT_SAMPLE_FACTORS":[ { "Subject ID":"-", "Sample ID":"ms5952-1", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"8/3/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-2", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"8/3/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-3", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"8/3/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-4", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"8/3/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-5", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"8/3/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-6", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"8/3/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-7", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"8/3/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-8", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"8/3/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-9", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"8/10/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-10", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"8/10/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-11", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"8/10/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-12", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"8/10/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-13", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"8/10/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-14", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"8/10/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-15", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"8/10/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-16", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"8/10/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-17", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-18", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-19", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-20", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-21", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-22", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-23", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-24", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-25", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-26", "Factors":{"Time point":"Control"}, "Additional sample data":{"Date of study":"9/2/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-27", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-28", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-29", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-30", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-31", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-32", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-33", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"M","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-34", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-35", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"F","sample source":"rat urine"} }, { "Subject ID":"-", "Sample ID":"ms5952-36", "Factors":{"Time point":"7 day HS"}, "Additional sample data":{"Date of study":"9/9/2010","gender":"F","sample source":"rat urine"} } ], "COLLECTION":{"COLLECTION_SUMMARY":"Samples are from Transgenic fumerase rats and WT littermates, 13 weeks of age, placed on low salt or high salt dyets. We are interested in any differences in the TCA and AA intermediates."}, "TREATMENT":{"TREATMENT_SUMMARY":"We will analyze kidney tissue extract and urine samples from SS rats and the newly generated SS.Fh1+ transgenic rats. The SS.Fh1+ rat was generated using a Sleeping Beauty transposon-mediated transgenic technique. Overexpression of fumarase has been confirmed in SS.Fh1+ rats. Preliminary study indicated that the development of salt-induced hypertension was altered in SS.Fh1+ rats compared to wild-type littermate SS rats. We will analyze kidney tissue extract and urine samples collected from rats maintained on a 0.4% NaCl diet or switched to a 4% NaCl diet for 7 days. The dietary protocol has been used in numerous studies to examine mechanisms underlying salt sensitivity including early responses (7 days) to salt in the SS model. In total, 64 rat samples (two rat strains, two salt levels, and 8 rats per condition) will be analyzed."}, "SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Rat urine TCA concentrations"}, "CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"GC","INSTRUMENT_NAME":"Agilent 7890A","COLUMN_NAME":"Agilent HP5-MS (30m × 0.25mm, 0.25 um)"}, "ANALYSIS":{"ANALYSIS_TYPE":"MS"}, "MS":{"MS_COMMENTS":"-","INSTRUMENT_NAME":"Agilent 5975C","INSTRUMENT_TYPE":"Single quadrupole","MS_TYPE":"EI","ION_MODE":"POSITIVE"}, "MS_METABOLITE_DATA":{ "Units":"uM", 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"Metabolites":[{"metabolite_name":"Lactate"},{"metabolite_name":"Succinate"},{"metabolite_name":"Fumarate"},{"metabolite_name":"Oxaloacetate"},{"metabolite_name":"Ketoglutarate"},{"metabolite_name":"Malate"},{"metabolite_name":"cis-Aconitate"},{"metabolite_name":"Citrate"},{"metabolite_name":"Isocitrate"}] } }