Summary of Study ST000584
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 PR000427. The data can be accessed directly via it's Project DOI: 10.21228/M8VK5D 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.
Study ID | ST000584 |
Study Title | Fasting wildtype, tfeb -/- knockout, and lmna -/- knockout metabolite profiling of adult zebrafish |
Study Summary | Inhibition of mechanistic target of rapamycin (mTOR) activity exerts cardioprotective functions. We propose to assess the metabolite profile in zebrafish cardiomyopathy models to test the cardioprotective role of mTOR-TFEB-autophagy and mTOR-lmna- autophagy signaling in heart, liver, muscle, brain, and kidney tissue. In addition mTOR signaling among zebrafish 2 hour post feeding, 24 hour post feeding, and 48 hour post feeding will be profiled. These studes will be used as a baseline and for protocol development before we assess changes in DOX-induced cardiomyopathy. |
Institute | Mayo Clinic |
Last Name | Xu |
First Name | Xiaolei |
Address | 200 First Street SW, Rochester, MN 55905 |
Xu.Xiaolei@mayo.edu | |
Phone | 507-284-0685 |
Submit Date | 2017-03-10 |
Analysis Type Detail | LC-MS |
Release Date | 2019-05-15 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
Project ID: | PR000427 |
Project DOI: | doi: 10.21228/M8VK5D |
Project Title: | Mayo Metabolomics Pilot and Feasibility Award: Deciphering cardioprotective effects of mTOR inhibition via metabolite profiling |
Project Summary: | Cardiomyopathy is the most common cause for sudden death and heart failure with tremendous public health burden in the U.S. Accumulating evidence from both animal models and clinical studies in human transplant patients suggests that partial inhibition of mechanistic Taget of Rapamycin (mTOR) signaling is a viable avenue for therapeutic intervention. Specifically, we recently showed both compound (rapamycin) treatment and genetic manipulation using a mechanistic Target of Rapamycin (mTOR) haploinsufficient (mTOR+/-) mutant confers cardiac protection against cardiomyopathies of two different etiologies in zebrafish. Mechanistically, antihypertrophy, anti-apoptosis and proautophagy of mTOR inhibition play important roles in this cardioprotection process. Our central hypothesis is that this mTOR inhibition-mediated cardioprotection is conferred by transcription factor EB (TFEB)-regulated autophagy activation. To test this hypothesis, we propose to pursue a systematic metabolite profiling analysis in the heart upon DOX stress under fine-tuned mTOR inhibition. We expect to define metabolite signatures in different types of cardiomyopathy, metabolite signature for the cardioprotective effects of mTOR inhibition, as well as metabolite signatures for TFEB genetic manipulations. These data will be compared with transcriptome studies to prove functions of TFEB signaling in cardioprotective effects of mTOR inhibition, which shall provide a solid foundation for renewing our current RO1 grant aiming to develop mTOR-based therapy for heart failure. |
Institute: | Mayo Clinic |
Last Name: | Xu |
First Name: | Xiaolei |
Address: | 200 First Street SW, Rochester, MN 55905 |
Email: | Xu.Xiaolei@mayo.edu |
Phone: | 507-284-0685 |
Subject:
Subject ID: | SU000607 |
Subject Type: | Zebrafish |
Subject Species: | Danio rerio |
Taxonomy ID: | 7955 |
Species Group: | Fish |
Factors:
Subject type: Zebrafish; Subject species: Danio rerio (Factor headings shown in green)
mb_sample_id | local_sample_id | sex | tissue | timepoint | genotype |
---|---|---|---|---|---|
SA030858 | nC18-20nov15-020-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030859 | nC18-20nov15-018-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030860 | nC18-20nov15-020-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030861 | nC18-20nov15-018-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030862 | nC18-20nov15-022-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030863 | nC18-20nov15-025-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030864 | nC18-20nov15-025-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030865 | pC18-18nov15-025-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030866 | nhilic-19nov15-025-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030867 | nhilic-19nov15-025-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030868 | nhilic-19nov15-020-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030869 | nhilic-19nov15-020-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030870 | nhilic-19nov15-018-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030871 | nhilic-19nov15-022-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030872 | nhilic-19nov15-022-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030873 | nC18-20nov15-005-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030874 | nC18-20nov15-005-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030875 | philic-18nov15-005-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030876 | philic-18nov15-005-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030877 | pC18-18nov15-018-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030878 | pC18-18nov15-018-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030879 | pC18-18nov15-005-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030880 | pC18-18nov15-020-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030881 | pC18-18nov15-020-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030882 | pC18-18nov15-025-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030883 | pC18-18nov15-022-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030884 | pC18-18nov15-022-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030885 | pC18-18nov15-005-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030886 | philic-18nov15-018-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030887 | philic-18nov15-022-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030888 | philic-18nov15-025-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030889 | philic-18nov15-025-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030890 | philic-18nov15-022-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030891 | philic-18nov15-020-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030892 | philic-18nov15-018-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030893 | philic-18nov15-020-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030894 | nhilic-19nov15-018-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030895 | nC18-20nov15-022-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030896 | nhilic-19nov15-005-r001 | female | heart | tfeb-/- | tfeb-/- |
SA030897 | nhilic-19nov15-005-r002 | female | heart | tfeb-/- | tfeb-/- |
SA030898 | nC18-26nov15-023-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030899 | nC18-26nov15-023-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030900 | philic-24nov15-005-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030901 | pC18-24nov15-023-r002_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030902 | philic-24nov15-015-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030903 | philic-24nov15-017-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030904 | philic-24nov15-017-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030905 | philic-24nov15-015-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030906 | nhilic-25nov15-012-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030907 | nhilic-25nov15-012-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030908 | nhilic-25nov15-017-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030909 | nhilic-25nov15-017-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030910 | nhilic-25nov15-015-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030911 | nhilic-25nov15-023-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030912 | philic-24nov15-005-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030913 | philic-24nov15-023-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030914 | philic-24nov15-023-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030915 | nhilic-25nov15-023-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030916 | nhilic-25nov15-005-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030917 | pC18-24nov15-017-r002_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030918 | nC18-26nov15-005-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030919 | nC18-26nov15-015-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030920 | nC18-26nov15-015-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030921 | nC18-26nov15-017-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030922 | nC18-26nov15-005-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030923 | pC18-24nov15-005-r002_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030924 | nC18-26nov15-012-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030925 | nC18-26nov15-012-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030926 | pC18-24nov15-005-r001_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030927 | pC18-24nov15-012-r001_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030928 | nC18-26nov15-017-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030929 | philic-24nov15-012-r002 | female | kidney | tfeb-/- | tfeb-/- |
SA030930 | nhilic-25nov15-005-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030931 | nhilic-25nov15-015-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030932 | pC18-24nov15-017-r001_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030933 | pC18-24nov15-015-r002_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030934 | philic-24nov15-012-r001 | female | kidney | tfeb-/- | tfeb-/- |
SA030935 | pC18-24nov15-012-r002_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030936 | pC18-24nov15-015-r001_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030937 | pC18-24nov15-023-r001_1 | female | kidney | tfeb-/- | tfeb-/- |
SA030938 | pC18-11nov15-019-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030939 | pC18-11nov15-022-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030940 | nhilic-12nov15-015-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030941 | nhilic-12nov15-015-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030942 | pC18-11nov15-022-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030943 | pC18-11nov15-019-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030944 | pC18-11nov15-016-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030945 | pC18-11nov15-016-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030946 | pC18-11nov15-015-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030947 | pC18-11nov15-003-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030948 | philic-11nov15-016-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030949 | philic-11nov15-016-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030950 | philic-11nov15-015-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030951 | philic-11nov15-015-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030952 | philic-11nov15-003-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030953 | philic-11nov15-003-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030954 | philic-11nov15-019-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030955 | philic-11nov15-019-r002 | female | muscle | tfeb-/- | tfeb-/- |
SA030956 | nhilic-12nov15-003-r001 | female | muscle | tfeb-/- | tfeb-/- |
SA030957 | nhilic-12nov15-003-r002 | female | muscle | tfeb-/- | tfeb-/- |
Collection:
Collection ID: | CO000601 |
Collection Summary: | When testing the wildtype fasting fish, we only choose male fish. For each of the 3 time points, we scarifice 25 fish, put 5 tissue in one tube for 5 repeats. Because of tissue size, I adjusted heart sample at 2h and kidney sample at 2h to 3 repeats, liver sample at 2h to 4 repeats. For tfeb-/-fish, we collected heart, muscle, kidney with each of them 5 repeats. We collected both male and female. For lmna-/- we collected heart and muscle(only male) with each 3 repeats. |
Sample Type: | Blood |
Treatment:
Treatment ID: | TR000621 |
Treatment Summary: | This is pre-test study for protocal development and baseline measures. Fish hearts are small, and more than 30 adult fish heart might need to be pooled to generated sufficient sample for a metabolic profiling experiments. Therefore, we will first test the condition using wild type fish at 3 months for this purpose. Tfeb -/- knockouts and lmna -/- knockouts are similarily being used for protocal development. After we optimize the protocol, we will assess changes in DOX-induced cardiomyopathy. |
Sample Preparation:
Sampleprep ID: | SP000614 |
Sampleprep Summary: | Handling of tissue 1) Keep tubes on ice for 10 min. Spin down @ 1000 RCF for 30 sec 2) Add 20 ul PBS per sample and 3 ul 13C6-Phe 3) Sonicate on ice bath for 30 sec x 4 times 4) Add 250 ul ACN/MeOH mixture and incubate on ice for 30 min 5) Pool 20 ul sup from each sample and split 100 ul pool in 5 tubes 6) Split remaining sup in two 1 dram vials x 2 (100 ul per vial) 7) Dry under N2 stream |
Combined analysis:
Analysis ID | AN000896 | AN000897 | AN000898 | AN000899 |
---|---|---|---|---|
Analysis type | MS | MS | MS | MS |
Chromatography type | HILIC | HILIC | Reversed phase | Reversed phase |
Chromatography system | Agilent 1290 Infinity | Agilent 1290 Infinity | Agilent 1290 Infinity | Agilent 1290 Infinity |
Column | Waters Acquity BEH Amide (150 x 2.1mm,1.7um) | Waters Acquity BEH Amide (150 x 2.1mm,1.7um) | Waters Acquity HSS C18 (150 x 2.1mm,1.8um) | Waters Acquity HSS C18 (150 x 2.1mm,1.8um) |
MS Type | ESI | ESI | ESI | ESI |
MS instrument type | QTOF | QTOF | QTOF | QTOF |
MS instrument name | Agilent 6550 QTOF | Agilent 6550 QTOF | Agilent 6550 QTOF | Agilent 6550 QTOF |
Ion Mode | POSITIVE | NEGATIVE | POSITIVE | NEGATIVE |
Units | unspecified | unspecified | unspecified | unspecified |
Chromatography:
Chromatography ID: | CH000638 |
Instrument Name: | Agilent 1290 Infinity |
Column Name: | Waters Acquity BEH Amide (150 x 2.1mm,1.7um) |
Chromatography Type: | HILIC |
Chromatography ID: | CH000639 |
Instrument Name: | Agilent 1290 Infinity |
Column Name: | Waters Acquity HSS C18 (150 x 2.1mm,1.8um) |
Chromatography Type: | Reversed phase |
MS:
MS ID: | MS000798 |
Analysis ID: | AN000896 |
Instrument Name: | Agilent 6550 QTOF |
Instrument Type: | QTOF |
MS Type: | ESI |
Ion Mode: | POSITIVE |
MS ID: | MS000799 |
Analysis ID: | AN000897 |
Instrument Name: | Agilent 6550 QTOF |
Instrument Type: | QTOF |
MS Type: | ESI |
Ion Mode: | NEGATIVE |
MS ID: | MS000800 |
Analysis ID: | AN000898 |
Instrument Name: | Agilent 6550 QTOF |
Instrument Type: | QTOF |
MS Type: | ESI |
Ion Mode: | POSITIVE |
MS ID: | MS000801 |
Analysis ID: | AN000899 |
Instrument Name: | Agilent 6550 QTOF |
Instrument Type: | QTOF |
MS Type: | ESI |
Ion Mode: | NEGATIVE |