Summary of Study ST000604

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000328. The data can be accessed directly via it's Project DOI: 10.21228/M8MK6M This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST000604
Study TitleImpact Of High Sugar Diet On L-Arginine Metabolism In The Lung (part II)
Study SummaryAsthma is a progressive inflammatory airways disease that leads to structural airway changes and debilitating symptoms in many severely affected adults. We need novel therapeutic agents that are affordable, can decrease the reliance on steroids, and can improve quality of life. This clinical and mechanistic study has the potential to impact treatment of a subset of adult severe asthmatics and to further our understanding of the mechanisms of L-arginine metabolism and NO biology in the airways of asthmatics. We will pursue a clinical trial in subjects not well controlled on standard drug therapy; this strategy will address whether L-arginine is efficacious in patients receiving standard of care medications. In studies using animal models, we and others have shown that interventions that augment NO levels, through either supplementation of L-arginine or inhibition of arginase, decrease allergic airway inflammation and hyperresponsiveness-the two hallmarks of asthma. Overall, we hypothesize that a responder subset of adult severe asthma patients will derive clinical benefit from supplemental L-arginine therapy and that these patients will have a lower exhaled NO concentrations (<20 ppb) and a higher NOS2/Arg1 mRNA and protein ratio in their airway epithelial cells than non-responders. We aim to: 1) test the hypothesis that uncontrolled, adult severe asthma patients with exhaled breath NO concentrations <20 ppb will have fewer asthma exacerbations over 3 months when treated with L-arginine compared to patients with FeNO > 25, 2) determine the mechanisms by which L-arginine affects the regulation of NOS and arginase enzymes in primary airway epithelial cell cultures from severe asthmatic subjects, and 3) test the hypothesis that inhaled nanoparticle carrier formulations of L-arginine will decrease airway inflammation, airway hyperresponsiveness, and airway fibrosis at lower doses than systemically administered L-arginine. The major impact of our study will be to identify the adult severe asthma cohort that will benefit from supplemental L-arginine therapy. Our ultimate goal is to develop novel therapeutic agents to treat adult severe asthma patients better. PUBLIC HEALTH RELEVANCE: Asthma is a progressive inflammatory airways disease that leads to structural airway changes and debilitating symptoms in many severely affected adults. This clinical study has the potential to improve the care of adult severe asthmatics and to further our understanding of the mechanisms of L-arginine metabolism and nitric oxide biology in the lung. If we demonstrate that L-arginine supplementation can decrease asthma attacks in a subset of severe asthmatics, it will have great implications for future research as well as for the daily lives of patients with asthma.
Institute
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Emailofiehn@ucdavis.edu
Phone(530) 754-8258
Submit Date2017-04-27
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2017-07-10
Release Version1
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M8MK6M
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000328
Project DOI:doi: 10.21228/M8MK6M
Project Title:Impact Of High Sugar Diet On L-Arginine Metabolism In The Lung
Project Summary:Asthma is a progressive inflammatory airways disease that leads to structural airway changes and debilitating symptoms in many severely affected adults. We need novel therapeutic agents that are affordable, can decrease the reliance on steroids, and can improve quality of life. This clinical and mechanistic study has the potential to impact treatment of a subset of adult severe asthmatics and to further our understanding of the mechanisms of L-arginine metabolism and NO biology in the airways of asthmatics. We will pursue a clinical trial in subjects not well controlled on standard drug therapy; this strategy will address whether L-arginine is efficacious in patients receiving standard of care medications. In studies using animal models, we and others have shown that interventions that augment NO levels, through either supplementation of L-arginine or inhibition of arginase, decrease allergic airway inflammation and hyperresponsiveness-the two hallmarks of asthma. Overall, we hypothesize that a responder subset of adult severe asthma patients will derive clinical benefit from supplemental L-arginine therapy and that these patients will have a lower exhaled NO concentrations (<20 ppb) and a higher NOS2/Arg1 mRNA and protein ratio in their airway epithelial cells than non-responders. We aim to: 1) test the hypothesis that uncontrolled, adult severe asthma patients with exhaled breath NO concentrations <20 ppb will have fewer asthma exacerbations over 3 months when treated with L-arginine compared to patients with FeNO > 25, 2) determine the mechanisms by which L-arginine affects the regulation of NOS and arginase enzymes in primary airway epithelial cell cultures from severe asthmatic subjects, and 3) test the hypothesis that inhaled nanoparticle carrier formulations of L-arginine will decrease airway inflammation, airway hyperresponsiveness, and airway fibrosis at lower doses than systemically administered L-arginine. The major impact of our study will be to identify the adult severe asthma cohort that will benefit from supplemental L-arginine therapy. Our ultimate goal is to develop novel therapeutic agents to treat adult severe asthma patients better. PUBLIC HEALTH RELEVANCE: Asthma is a progressive inflammatory airways disease that leads to structural airway changes and debilitating symptoms in many severely affected adults. This clinical study has the potential to improve the care of adult severe asthmatics and to further our understanding of the mechanisms of L-arginine metabolism and nitric oxide biology in the lung. If we demonstrate that L-arginine supplementation can decrease asthma attacks in a subset of severe asthmatics, it will have great implications for future research as well as for the daily lives of patients with asthma.
Institute:University of California, Davis
Department:Genome and Biomedical Sciences Facility
Laboratory:WCMC Metabolomics Core
Last Name:Fiehn
First Name:Oliver
Address:1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Email:ofiehn@ucdavis.edu
Phone:(530) 754-8258
Funding Source:NIH U24DK097154

Subject:

Subject ID:SU000627
Subject Type:Animal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male
Species Group:Mammal

Factors:

Subject type: Animal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Source Species Treatment
SA033314Inj017_CSH_Kid_CF78.dKidney Mouse Control Diet
SA033315Inj031_CSH_Kid_CF26.dKidney Mouse Control Diet
SA033316Inj016_CSH_Kid_CF54.dKidney Mouse Control Diet
SA033317Inj018_CSH_Kid_CF49.dKidney Mouse Control Diet
SA033318Inj029_CSH_Kid_CF70.dKidney Mouse Control Diet
SA033319Inj038_CSH_Kid_CF11.dKidney Mouse Control Diet
SA033320Inj028_CSH_Kid_CF82.dKidney Mouse Control Diet
SA033321Inj026_CSH_Kid_CF57.dKidney Mouse Control Diet
SA033322Inj014_CSH_Kid_CF90.dKidney Mouse Control Diet
SA033323Inj019_CSH_Kid_HFS82.dKidney Mouse High Fat Diet
SA033324Inj020_CSH_Kid_HFS1.dKidney Mouse High Fat Diet
SA033325Inj012_CSH_Kid_HFS59.dKidney Mouse High Fat Diet
SA033326Inj036_CSH_Kid_HFS55.dKidney Mouse High Fat Diet
SA033327Inj013_CSH_Kid_HFS70.dKidney Mouse High Fat Diet
SA033328Inj034_CSH_Kid_HFS87.dKidney Mouse High Fat Diet
SA033329Inj032_CSH_Kid_HFS69.dKidney Mouse High Fat Diet
SA033330Inj027_CSH_Kid_VHF64.dKidney Mouse Very High Fat Diet
SA033331Inj037_CSH_Kid_VHF70.dKidney Mouse Very High Fat Diet
SA033332Inj030_CSH_Kid_VHF86.dKidney Mouse Very High Fat Diet
SA033333Inj035_CSH_Kid_VHF31.dKidney Mouse Very High Fat Diet
SA033334Inj025_CSH_Kid_VHF80.dKidney Mouse Very High Fat Diet
SA033335Inj021_CSH_Kid_VHF45.dKidney Mouse Very High Fat Diet
SA033336Inj023_CSH_Kid_VHF92.dKidney Mouse Very High Fat Diet
SA033337Inj015_CSH_Kid_VHF97.dKidney Mouse Very High Fat Diet
SA033338Inj024_CSH_Kid_VHF2.dKidney Mouse Very High Fat Diet
SA033339Inj091_CSH_Liv_CF82.dLiver Mouse Control Diet
SA033340Inj079_CSH_Liv_CF57.dLiver Mouse Control Diet
SA033341Inj072_CSH_Liv_CF78.dLiver Mouse Control Diet
SA033342Inj090_CSH_Liv_CF11.dLiver Mouse Control Diet
SA033343Inj084_CSH_Liv_CF49.dLiver Mouse Control Diet
SA033344Inj092_CSH_Liv_CF90.dLiver Mouse Control Diet
SA033345Inj088_CSH_Liv_CF54.dLiver Mouse Control Diet
SA033346Inj085_CSH_Liv_CF70.dLiver Mouse Control Diet
SA033347Inj083_CSH_Liv_HFS87.dLiver Mouse High Fat Diet
SA033348Inj082_CSH_Liv_HFS69.dLiver Mouse High Fat Diet
SA033349Inj077_CSH_Liv_HFS59.dLiver Mouse High Fat Diet
SA033350Inj071_CSH_Liv_HFS82.dLiver Mouse High Fat Diet
SA033351Inj068_CSH_Liv_HFS55.dLiver Mouse High Fat Diet
SA033352Inj093_CSH_Liv_HFS92.dLiver Mouse High Fat Diet
SA033353Inj069_CSH_Liv_HFS1.dLiver Mouse High Fat Diet
SA033354Inj087_CSH_Liv_VHF80.dLiver Mouse Very High Fat Diet
SA033355Inj080_CSH_Liv_VHF92.dLiver Mouse Very High Fat Diet
SA033356Inj081_CSH_Liv_VHF97.dLiver Mouse Very High Fat Diet
SA033357Inj086_CSH_Liv_VHF70.dLiver Mouse Very High Fat Diet
SA033358Inj075_CSH_Liv_VHF31.dLiver Mouse Very High Fat Diet
SA033359Inj076_CSH_Liv_VHF45.dLiver Mouse Very High Fat Diet
SA033360Inj073_CSH_Liv_VHF2.dLiver Mouse Very High Fat Diet
SA033361Inj070_CSH_Liv_VHF64.dLiver Mouse Very High Fat Diet
SA033362Inj074_CSH_Liv_VHF86.dLiver Mouse Very High Fat Diet
SA033363Inj044_CSH_Lung_CF90.dLung Mouse Control Diet
SA033364Inj045_CSH_Lung_CF82.dLung Mouse Control Diet
SA033365Inj054_CSH_Lung_CF49.dLung Mouse Control Diet
SA033366Inj041_CSH_Lung_CF54.dLung Mouse Control Diet
SA033367Inj053_CSH_Lung_CF70.dLung Mouse Control Diet
SA033368Inj058_CSH_Lung_CF78.dLung Mouse Control Diet
SA033369Inj062_CSH_Lung_CF11.dLung Mouse Control Diet
SA033370Inj066_CSH_Lung_CF26.dLung Mouse Control Diet
SA033371Inj060_CSH_Lung_CF57.dLung Mouse Control Diet
SA033372Inj064_CSH_Lung_HFS70.dLung Mouse High Fat Diet
SA033373Inj065_CSH_Lung_HFS1.dLung Mouse High Fat Diet
SA033374Inj048_CSH_Lung_HFS87.dLung Mouse High Fat Diet
SA033375Inj056_CSH_Lung_HFS59.dLung Mouse High Fat Diet
SA033376Inj040_CSH_Lung_HFS55.dLung Mouse High Fat Diet
SA033377Inj059_CSH_Lung_HFS69.dLung Mouse High Fat Diet
SA033378Inj042_CSH_Lung_HFS82.dLung Mouse High Fat Diet
SA033379Inj057_CSH_Lung_HFS92.dLung Mouse High Fat Diet
SA033380Inj052_CSH_Lung_VHF86.dLung Mouse Very High Fat Diet
SA033381Inj055_CSH_Lung_VHF92.dLung Mouse Very High Fat Diet
SA033382Inj063_CSH_Lung_VHF64.dLung Mouse Very High Fat Diet
SA033383Inj046_CSH_Lung_VHF80.dLung Mouse Very High Fat Diet
SA033384Inj043_CSH_Lung_VHF2.dLung Mouse Very High Fat Diet
SA033385Inj051_CSH_Lung_VHF70.dLung Mouse Very High Fat Diet
SA033386Inj047_CSH_Lung_VHF31.dLung Mouse Very High Fat Diet
SA033387Inj049_CSH_Lung_VHF45.dLung Mouse Very High Fat Diet
SA033388Inj096_CSH_QC_10.dPlasma Human None
SA033389Inj089_CSH_QC_09.dPlasma Human None
SA033390Inj022_CSH_QC_02.dPlasma Human None
SA033391Inj078_CSH_QC_08.dPlasma Human None
SA033392Inj011_CSH_QC_01.dPlasma Human None
SA033393Inj050_CSH_QC_05.dPlasma Human None
SA033394Inj033_CSH_QC_03.dPlasma Human None
SA033395Inj039_CSH_QC_04.dPlasma Human None
SA033396Inj061_CSH_QC_06.dPlasma Human None
SA033397Inj067_CSH_QC_07.dPlasma Human None
Showing results 1 to 84 of 84

Collection:

Collection ID:CO000621
Collection Summary:C57BL/6 mice, 6-7 weeks of age upon diet assignment were fed for 150 days and weighed daily. Mice were euthanized with an overdose of pentobarbital IP and lungs were flash frozen. 6 mg of lung tissue was extracted for GC-TOFMS and HILIC-QTOFMS analysis.
Sample Type:Tissue

Treatment:

Treatment ID:TR000641
Treatment Summary:Male C57BL/6N mice (6-7 weeks of age) were provided ad libitum access to one of three diets for 150 days: low fat (10% kcals) control (CTRL) chow, high fat (45% kcals) with sugar (HFS) chow or very high (60% kcals) fat (VHF) chow. Body weight and food intake were measured daily.
Treatment Doseduration:150 Days

Sample Preparation:

Sampleprep ID:SP000634
Sampleprep Summary:1. Weigh 50 mg tissue sample in to a 25 ml conical polypropylene centrifuge tube. 2. Add 2.5mL extraction solvent to the tissue sample and homogenize for 45 seconds ensuring that sample resembles a powder. In between samples, clean the homogenizer in solutions of methanol, acetone, water, and the extraction solvent. 3. Centrifuge the samples at 2500 rpm. for 5 minutes. Aliquot 2 X 500μl supernatant, one for analysis and one for a backup sample. Store backup aliquot in the -20°C freezer. 4. Evaporate one 500μl aliquot of the sample in the Labconco Centrivap cold trap concentrator to complete dryness 5. The dried aliquot is then re-suspended with 500l 50% acetonitrile (degassed as given) 6. Centrifuge for 2 min at 14000 rcf using the centrifuge Eppendorf 5415. 7. Remove supernatant to a new Eppendorff tube. 8. Evaporate the supernatant to dryness in the the Labconco Centrivap cold trap concentrator. 9. Submit to derivatization.
Sampleprep Protocol Filename:SOP_Extraction_of_Mammalian_Tissue_Samples.pdf
Sampleprep Protocol Comments:This study combined 2 different injection volumes for certain samples when processing positive mode data. The reason for this was because in certain samples the TG's were overloaded with the 1uL injections, but everything else was at a normal peak height. Therefore samples were run at a 0.1uL injection volume and took the data from 9-12.5 minutes because that's when TG's elute. The samples that were injected at 0.1uL were used for times 9 min-12.5 min and the 1uL samples were used for times 0-8.99min.

Combined analysis:

Analysis ID AN000924 AN000925
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Agilent 6530 Agilent 6550
Column Waters Acquity CSH C18 (100 x 2.1mm,1.7um) Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
MS Type ESI ESI
MS instrument type QTOF QTOF
MS instrument name Agilent 6530 QTOF Agilent 6550 QTOF
Ion Mode POSITIVE NEGATIVE
Units Counts Counts

Chromatography:

Chromatography ID:CH000660
Chromatography Summary:See file below.
Methods Filename:Data_Dictionary_Fiehn_laboratory_CSH_QTOF_lipidomics_05-29-2014.pdf
Instrument Name:Agilent 6530
Column Name:Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
Column Pressure:450-850 bar
Column Temperature:65 C
Flow Gradient:15% B to 99% B
Flow Rate:0.6 mL/min
Injection Temperature:4 C
Internal Standard:See data dictionary
Retention Time:See data dictionary
Sample Injection:1.67 uL
Solvent A:60% acetonitrile/40% water; 10mM formic acid; 10mM ammonium formate
Solvent B:90% isopropanol/10% acetonitrile; 10mM formic acid; 10mM ammonium formate
Analytical Time:13 min
Capillary Voltage:3500
Time Program:15 min
Weak Wash Solvent Name:Isopropanol
Strong Wash Solvent Name:Isopropanol
Target Sample Temperature:Autosampler temp 4 C
Randomization Order:Excel
Chromatography Type:Reversed phase
  
Chromatography ID:CH000661
Chromatography Summary:See file below
Methods Filename:Data_Dictionary_Fiehn_laboratory_CSH_QTOF_lipidomics_05-29-2014.pdf
Instrument Name:Agilent 6550
Column Name:Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
Column Pressure:450-850 bar
Column Temperature:65 C
Flow Gradient:15% B to 99% B
Flow Rate:0.6 mL/min
Injection Temperature:4 C
Internal Standard:See data dictionary
Retention Time:See data dictionary
Sample Injection:5.0 uL
Solvent A:60% acetonitrile/40% water; 10 mM ammonium acetate; 10mM acetic acid formate; 10mM formic acid
Solvent B:90% isopropanol/10% acetonitrile; 10mM acetic acid; 10mM ammonium acetate
Analytical Time:13 min
Capillary Voltage:3500
Time Program:15 min
Weak Wash Solvent Name:Isopropanol
Strong Wash Solvent Name:Isopropanol
Target Sample Temperature:Autosampler temp 4 C
Randomization Order:Excel
Chromatography Type:Reversed phase

MS:

MS ID:MS000822
Analysis ID:AN000924
Instrument Name:Agilent 6530 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:POSITIVE
Capillary Voltage:3500
Collision Energy:25 eV
Collision Gas:Nitrogen
Dry Gas Flow:8L/min
Dry Gas Temp:325 C
Fragment Voltage:120
Fragmentation Method:Auto MSMS
Ion Source Temperature:325 C
Ion Spray Voltage:1000
Ionization:Pos
Precursor Type:Intact Molecule
Reagent Gas:Nitrogen
Source Temperature:325 C
Dataformat:.d
Desolvation Gas Flow:11 L/min
Desolvation Temperature:350 C
Nebulizer:35 psig
Octpole Voltage:750
Resolution Setting:Exteded Dyamic Range
Scan Range Moverz:60-1700 Da
Scanning Cycle:2 Hz
Scanning Range:60-1700 Da
Skimmer Voltage:65
  
MS ID:MS000823
Analysis ID:AN000925
Instrument Name:Agilent 6550 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:NEGATIVE
Capillary Voltage:3500
Collision Energy:25 eV
Collision Gas:Nitrogen
Dry Gas Flow:13L/min
Dry Gas Temp:200 C
Fragment Voltage:175
Fragmentation Method:Auto MSMS
Ion Source Temperature:325 C
Ion Spray Voltage:1000
Ionization:Neg
Precursor Type:Intact Molecule
Reagent Gas:Nitrogen
Source Temperature:325 C
Dataformat:.d
Desolvation Gas Flow:11 L/min
Desolvation Temperature:350 C
Nebulizer:35 psig
Octpole Voltage:750
Resolution Setting:Exteded Dyamic Range
Scan Range Moverz:60-1700 Da
Scanning Cycle:2 Hz
Scanning Range:60-1700 Da
Skimmer Voltage:65
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