Summary of Study ST001635

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 PR001044. The data can be accessed directly via it's Project DOI: 10.21228/M8RD7H This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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 IDST001635
Study TitleHigher Dietary Carbohydrates Detrimentally Impact Obesity-Associated Breast Cancer Chemoresistance
Study TypeUntargeted UPLC-MS Metabolomics Analysis
Study SummaryThis study is a part of an ongoing project entitled, “Higher Dietary Carbohydrates Detrimentally Impact Obesity-Associated Breast Cancer Chemoresistance.” (See project). Untargeted LCMS metabolomics analysis was performed to identify metabolic markers of nutritionally dependent and obesity-associated chemoresistance in female C57LB/6 mice fed either a high carbohydrate plus high fat (HCHF) diet or a high protein diet (HP). Mice were fed 15 weeks on either diet, then injected with a MMTV-Wnt-1 mouse mammary basal-like breast cancer cell line, for tumor formation up to 6 weeks. Three mice on either diet were treated for 24 hr with Doxorubicin or Saline as a vehicle control. All samples were analyzed in the positive mode for untargeted metabolomics analysis. Liver samples were selected for analysis because of an observation of fatty liver development in mice only on the HCHF diet after 15 weeks. Samples were extracted and analyzed by UPLS-MS analysis using Q-Exactive HFX mass spectrometer.
Institute
University of North Carolina at Chapel Hill
DepartmentNutrition
LaboratoryMetabolomics and Exposome Laboratory, Nutrition Research Institute, UNC Chapel Hill
Last NameSumner
First NameSusan
Address500 Laureate Way, Nutrition Research Institute, UNC Chapel Hill
Emailsusan_sumner@unc.edu
Phone(919) 622-4456
Submit Date2020-12-18
Num Groups6
Total Subjects193
Num Females175
Study CommentsThe number of groups includes the QC samples
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2021-12-18
Release Version1
Susan Sumner Susan Sumner
https://dx.doi.org/10.21228/M8RD7H
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001044
Project DOI:doi: 10.21228/M8RD7H
Project Title:Higher Dietary Carbohydrates Detrimentally Impact Obesity-Associated Breast Cancer Chemoresistance
Project Type:C18 Reversed-Phase Broad Spectrum Metabolomics
Project Summary:Epidemiologic and experimental studies have established that obesity is an important risk and/or prognostic factor for most cancer types, but the mechanisms underlying the obesity-cancer link have not been clearly elucidated. The goal of this project is to address questions on the mechanisms of (and potential solutions to) obesity that results directly from diet exposures and the associated chemotherapeutic resistance. In a mouse model of basal-like breast cancer (BLBC), we compared a high protein (HP) diet to a high carbohydrate plus high fat (HCHF) diet and determined their comparative impacts on body weight, fatty liver development, tumor growth acute chemotherapy response to doxorubicin, profiled 80 inflammatory markers and performed untargeted metabolomics. Briefly, female C57BL/6 mice were fed either the HP or HCHF diet for 15 weeks, orthotopically implanted with MMTV-Wnt-1 mammary cells for tumor formation and growth (up to six weeks), then treated with a single dose of doxorubicin (or saline vehicle control) for 24 hours prior to study completion. Mice were euthanized and biospecimens were collected at the following study endpoints: 1-baseline (following 1-week quarantine); 2-after the 15 weeks of differential diet exposure; 3-after 5 weeks and 5.5 weeks of tumor growth; and 4-after 24 hours of treatment, corresponding to 6 weeks of tumor growth. Untargeted metabolomics analysis was performed by UPLC high resolution mass spectrometry (LCMS) on liver samples at the four study endpoints described above. Liver tissues were sectioned into three discrete lobes (right, left and median=caudate + quadrate) prior to analysis.
Institute:University of North Carolina at Chapel Hill
Department:Nutrition
Laboratory:Metabolomics and Exposome Laboratory, Nutrition Research Institute, UNC Chapel Hill
Last Name:Stewart
First Name:Delisha
Address:500 Laureate Way, Nutrition Research Institute, UNC Chapel Hill
Email:delisha_stewart@unc.edu
Phone:+1 (704) 250-5068

Subject:

Subject ID:SU001712
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/6
Gender:Female
Animal Animal Supplier:Charles River Labs
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Diet Study Phenotype Treatment Liver Lobe
SA138239L_26HCHF 15 wk Differential Diet None Left
SA138240L_29HCHF 15 wk Differential Diet None Left
SA138241L_41HCHF 15 wk Differential Diet None Left
SA138242L_32HCHF 15 wk Differential Diet None Left
SA138243L_35HCHF 15 wk Differential Diet None Left
SA138244L_44HCHF 15 wk Differential Diet None Left
SA138245L_38HCHF 15 wk Differential Diet None Left
SA138246L_47HCHF 15 wk Differential Diet None Left
SA138247L_27HCHF 15 wk Differential Diet None Median
SA138248L_36HCHF 15 wk Differential Diet None Median
SA138249L_39HCHF 15 wk Differential Diet None Median
SA138250L_33HCHF 15 wk Differential Diet None Median
SA138251L_48HCHF 15 wk Differential Diet None Median
SA138252L_42HCHF 15 wk Differential Diet None Median
SA138253L_45HCHF 15 wk Differential Diet None Median
SA138254L_30HCHF 15 wk Differential Diet None Median
SA138255L_43HCHF 15 wk Differential Diet None Right
SA138256L_40HCHF 15 wk Differential Diet None Right
SA138257L_46HCHF 15 wk Differential Diet None Right
SA138258L_25HCHF 15 wk Differential Diet None Right
SA138259L_28HCHF 15 wk Differential Diet None Right
SA138260L_37HCHF 15 wk Differential Diet None Right
SA138261L_31HCHF 15 wk Differential Diet None Right
SA138262L_34HCHF 15 wk Differential Diet None Right
SA138263L_146HCHF 24 hr Treatment DOX-treated Left
SA138264L_152HCHF 24 hr Treatment DOX-treated Left
SA138265L_149HCHF 24 hr Treatment DOX-treated Left
SA138266L_150HCHF 24 hr Treatment DOX-treated Median
SA138267L_153HCHF 24 hr Treatment DOX-treated Median
SA138268L_147HCHF 24 hr Treatment DOX-treated Median
SA138269L_145HCHF 24 hr Treatment DOX-treated Right
SA138270L_151HCHF 24 hr Treatment DOX-treated Right
SA138271L_148HCHF 24 hr Treatment DOX-treated Right
SA138272L_158HCHF 24 hr Treatment Saline-control Left
SA138273L_161HCHF 24 hr Treatment Saline-control Left
SA138274L_155HCHF 24 hr Treatment Saline-control Left
SA138275L_156HCHF 24 hr Treatment Saline-control Median
SA138276L_159HCHF 24 hr Treatment Saline-control Median
SA138277L_162HCHF 24 hr Treatment Saline-control Median
SA138278L_157HCHF 24 hr Treatment Saline-control Right
SA138279L_154HCHF 24 hr Treatment Saline-control Right
SA138280L_160HCHF 24 hr Treatment Saline-control Right
SA138287L_104HCHF Tumor Growth-5.5 wk None Left
SA138288L_89HCHF Tumor Growth-5.5 wk None Left
SA138289L_98HCHF Tumor Growth-5.5 wk None Left
SA138290L_86HCHF Tumor Growth-5.5 wk None Left
SA138291L_95HCHF Tumor Growth-5.5 wk None Left
SA138292L_101HCHF Tumor Growth-5.5 wk None Left
SA138293L_113HCHF Tumor Growth-5.5 wk None Left
SA138294L_110HCHF Tumor Growth-5.5 wk None Left
SA138295L_107HCHF Tumor Growth-5.5 wk None Left
SA138296L_92HCHF Tumor Growth-5.5 wk None Left
SA138297L_87HCHF Tumor Growth-5.5 wk None Median
SA138298L_96HCHF Tumor Growth-5.5 wk None Median
SA138299L_99HCHF Tumor Growth-5.5 wk None Median
SA138300L_114HCHF Tumor Growth-5.5 wk None Median
SA138301L_111HCHF Tumor Growth-5.5 wk None Median
SA138302L_108HCHF Tumor Growth-5.5 wk None Median
SA138303L_90HCHF Tumor Growth-5.5 wk None Median
SA138304L_105HCHF Tumor Growth-5.5 wk None Median
SA138305L_93HCHF Tumor Growth-5.5 wk None Median
SA138306L_94HCHF Tumor Growth-5.5 wk None Right
SA138307L_112HCHF Tumor Growth-5.5 wk None Right
SA138308L_109HCHF Tumor Growth-5.5 wk None Right
SA138309L_106HCHF Tumor Growth-5.5 wk None Right
SA138310L_103HCHF Tumor Growth-5.5 wk None Right
SA138311L_100HCHF Tumor Growth-5.5 wk None Right
SA138312L_97HCHF Tumor Growth-5.5 wk None Right
SA138313L_91HCHF Tumor Growth-5.5 wk None Right
SA138314L_85HCHF Tumor Growth-5.5 wk None Right
SA138315L_88HCHF Tumor Growth-5.5 wk None Right
SA138281L_77HCHF Tumor Growth-5 wk None Left
SA138282L_74HCHF Tumor Growth-5 wk None Left
SA138283L_78HCHF Tumor Growth-5 wk None Median
SA138284L_75HCHF Tumor Growth-5 wk None Median
SA138285L_76HCHF Tumor Growth-5 wk None Right
SA138286L_73HCHF Tumor Growth-5 wk None Right
SA138316L_56HP 15 wk Differential Diet None Left
SA138317L_68HP 15 wk Differential Diet None Left
SA138318L_59HP 15 wk Differential Diet None Left
SA138319L_62HP 15 wk Differential Diet None Left
SA138320L_65HP 15 wk Differential Diet None Left
SA138321L_71HP 15 wk Differential Diet None Left
SA138322L_53HP 15 wk Differential Diet None Left
SA138323L_50HP 15 wk Differential Diet None Left
SA138324L_51HP 15 wk Differential Diet None Median
SA138325L_63HP 15 wk Differential Diet None Median
SA138326L_60HP 15 wk Differential Diet None Median
SA138327L_66HP 15 wk Differential Diet None Median
SA138328L_57HP 15 wk Differential Diet None Median
SA138329L_72HP 15 wk Differential Diet None Median
SA138330L_69HP 15 wk Differential Diet None Median
SA138331L_54HP 15 wk Differential Diet None Median
SA138332L_61HP 15 wk Differential Diet None Right
SA138333L_52HP 15 wk Differential Diet None Right
SA138334L_49HP 15 wk Differential Diet None Right
SA138335L_55HP 15 wk Differential Diet None Right
SA138336L_58HP 15 wk Differential Diet None Right
SA138337L_67HP 15 wk Differential Diet None Right
SA138338L_70HP 15 wk Differential Diet None Right
Showing page 1 of 2     Results:    1  2  Next     Showing results 1 to 100 of 193

Collection:

Collection ID:CO001705
Collection Summary:See the project foe more details. Briefly, mice were euthanized and biospecimens were collected at the following study endpoints: 1-baseline (following 1-week quarantine); 2-after the 15 weeks of differential diet exposure; 3-after 5 weeks and 5.5 weeks of tumor growth; and 4-after 24 hours of treatment, corresponding to 6 weeks of tumor growth.
Sample Type:Liver
Storage Conditions:-80℃

Treatment:

Treatment ID:TR001725
Treatment Summary:24 hr single dose treatment with Doxorubicin or saline (vehicle control). See project for more details.
Treatment Dose:10 mg/kg
Treatment Dosevolume:100 uL
Treatment Doseduration:24 hr
Treatment Vehicle:saline

Sample Preparation:

Sampleprep ID:SP001718
Sampleprep Summary:Liver tissue samples were put into randomized order (n=60), then were weighed then sectioned into three lobes (on dry ice) prior to analyses. Tissues were sectioned into the Right lobe, Left lobe and Median lobe (comprised of the caudate+quadrate lobes). Individual lobe weights were measured, then each lobe was further sectioned into equal numbers of cubes (4-6 cubes/lobe), depending on the lobe size. Two-three smaller cubes, were recombined into a new tube, weighed and used for metabolomics analysis. Two mice (HP diet, 5.5 weeks of tumor growth) were missing both left and median lobes from their gross liver tissues, and one mouse (HCHF diet, 5.5 weeks of tumor growth) was missing the median lobe; thus these samples were not included for metabolomics analysis. Thus, the total number of experimental samples was 175 rather than 180.
Processing Method:Sectioned and weighed frozen liver tissue samples (n=175, 60-450 mg) were homogenized with cold methanol (10 µl for every mg of tissue) in a Bead Ruptor Elite Bead Mill Homogenizer (OMNI International) at 5.0 m/s for 30 s in two cycles. The supernatants were collected after centrifugation at 16,000 rcf for 20 min at 4 °C. A quality control pool (QC pool) sample was prepared by pooling 30 µL supernatant aliquots from selected individual samples (n=78), with a total pre-processing weight ≥ 60 mg. The supernatants (200 µL) of each study sample and QC pools were transferred to new tubes and dried under Speed-vac. Each dried sample was reconstituted in a 200 µL water-methanol (95:5) solution containing 500 ng/ml L-tryphotophan-d5. The samples were thoroughly mixed on multiple tube vortexer for 10 mins at 5000 rpm. Samples were centrifuged at room temperature and at 16,000 rcf for 4 min. The supernatant was transferred to pre-labeled auto-sampler vials for data acquisition. Untargeted metabolomics was conducted using a Thermo Scientific™ Vanquish™ UPHPLC - Q Exactive™ HF-X Orbitrap System. Metabolites were separated on an Acquity UPLC HSS T3 C18 (2.1 X 100 mm, 1.8 µm) operating at 50 °C using a reversed phase gradient separation with Water with 0.1% Formic Acid (v/v) as mobile phase A and Methanol with 0.1% Formic Acid (v/v) as mobile phase B. A 5 µL amount was injected into the instrument, and MS data was collected between 50-750 m/z in the positive mode with the MS/MS data triggered by the Data-Dependent Acquisition.
Processing Storage Conditions:4℃
Extract Storage:-80℃

Combined analysis:

Analysis ID AN002672
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Vanquish
Column Waters Acquity BEH HSS T3 (100 x 2.1mm,1.8um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive HF hybrid Orbitrap
Ion Mode POSITIVE
Units peak area

Chromatography:

Chromatography ID:CH001966
Chromatography Summary:None
Chromatography Comments:Time(min) Flow Rate %A %B Curve 1. 0 0.4 99.0 1.0 5 2. 1.00 0.4 99.0 1.0 5 3. 16.00 0.4 1.0 99.0 5 4. 19.00 0.4 1.0 99.0 5 5. 19.50 0.4 99.0 1.0 5
Instrument Name:Thermo Vanquish
Column Name:Waters Acquity BEH HSS T3 (100 x 2.1mm,1.8um)
Column Pressure:6000-10000
Column Temperature:8
Flow Rate:0.4 mL/min
Injection Temperature:8
Solvent A:100% water; 0.1% formic acid
Solvent B:100% methanol; 0.1% formic acid
Weak Wash Solvent Name:10:90 Methanol:Water with 0.1% FA solution
Strong Wash Solvent Name:75:25 2-Propanol: Water with 0.1% FA solution
Randomization Order:Yes
Chromatography Type:Reversed phase

MS:

MS ID:MS002471
Analysis ID:AN002672
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:NA
Ion Mode:POSITIVE
Capillary Temperature:275 °C
Capillary Voltage:3.5 KV
Collision Energy:10-35, ramp
Collision Gas:N2
Dry Gas Flow:45
Dry Gas Temp:325°C
Fragmentation Method:CID
Desolvation Gas Flow:45
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