Summary of Study ST003495
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 PR002144. The data can be accessed directly via it's Project DOI: 10.21228/M8GR8V 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 | ST003495 |
| Study Title | Hepatocyte Period 1 dictates oxidative substrate selection independent of the core circadian clock |
| Study Summary | Organisms integrate circadian and metabolic signals to optimize substrate selection to survive starvation. Yet, precisely how this occurs is unclear. Here, we show that hepatocyte Period1 is selectively induced during fasting, and mice lacking hepatocyte Per1 fail to initiate autophagic flux, ketogenesis and lipid accumulation. Transcriptomic analyses show failed induction of the fasting hepatokine Fgf21 in Per1-deficient mice, and single-nucleus multiomic reveals a putative responding hepatocyte subpopulation that fails to induce the chromatin accessibility near the Fgf21 locus. In vivo isotopic tracing and indirect calorimetry demonstrate hepatocyte Per1-deficient mice fail to transit from oxidation of glucose to fat, which was completely reversible by exogenous FGF21, or by inhibiting pyruvate dehydrogenase. Strikingly, disturbing other core circadian genes does not perturb Per1 induction during fasting. We thus describe Per1 as an important mechanism by which hepatocytes integrate internal circadian rhythm and external nutrition signals to facilitate proper fuel utilization. |
| Institute | Washington University in St. Louis |
| Last Name | Sun |
| First Name | Jiameng |
| Address | 660 S. Euclid Ave |
| jiameng@wustl.edu | |
| Phone | 3149349954 |
| Submit Date | 2024-09-24 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | Other |
| Release Date | 2024-09-25 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002144 |
| Project DOI: | doi: 10.21228/M8GR8V |
| Project Title: | Hepatocyte Period 1 dictates oxidative substrate selection independent of the core circadian clock |
| Project Summary: | In this project we quantified the extent to which exogenously administered FGF21 reconstitutes substrate selection observed in fasting Per1iLKO mice. We treated Per1fl/fl or Per1iLKO mice with or without recombinant FGF21 protein after a 14 h + 2 h fast/refeed, and subjected them to heavy isotope metabolic tracing in vivo. Although we observed no significant defects found in total hepatic metabolites involved in glycolysis and PDH-mediated pathway in Per1iLKO mice during refeeding, [13C6]-glucose tracing revealed increased labeling in the glycolytic and PDH-mediated TCA cycle in fasting Per1iLKO mice. Moreover, treatment with recombinant FGF21 significantly reduced glycolytic and PDH-mediated TCA cycle flux in Per1iLKO mice, but did not drive significant changes in fasting Per1fl/fl mice. |
| Institute: | Washington University in St. Louis |
| Last Name: | Sun |
| First Name: | Jiameng |
| Address: | 660 S. Euclid Ave |
| Email: | jiameng@wustl.edu |
| Phone: | 3149349954 |
Subject:
| Subject ID: | SU003623 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment | Sample source |
|---|---|---|---|
| SA385452 | DBLiver_pP_6C | LKO_Fast_FGF21 | Mouse liver |
| SA385453 | DBLiver_nP_6D | LKO_Fast_FGF21 | Mouse liver |
| SA385454 | DBLiver_nP_6C | LKO_Fast_FGF21 | Mouse liver |
| SA385455 | DBLiver_pP_6E | LKO_Fast_FGF21 | Mouse liver |
| SA385456 | DBLiver_pP_6D | LKO_Fast_FGF21 | Mouse liver |
| SA385457 | DBLiver_nP_6E | LKO_Fast_FGF21 | Mouse liver |
| SA385458 | DBLiver_pP_6A | LKO_Fast_Refeed | Mouse liver |
| SA385459 | DBLiver_nP_6B | LKO_Fast_Refeed | Mouse liver |
| SA385460 | DBLiver_pP_6B | LKO_Fast_Refeed | Mouse liver |
| SA385461 | DBLiver_nP_6A | LKO_Fast_Refeed | Mouse liver |
| SA385462 | DBLiver_pP_5B | LKO_Fast | Mouse liver |
| SA385463 | DBLiver_pP_5A | LKO_Fast | Mouse liver |
| SA385464 | DBLiver_pP_4A | LKO_Fast | Mouse liver |
| SA385465 | DBLiver_nP_4A | LKO_Fast | Mouse liver |
| SA385466 | DBLiver_nP_5A | LKO_Fast | Mouse liver |
| SA385467 | DBLiver_nP_5B | LKO_Fast | Mouse liver |
| SA385468 | DBLiver_pP_3B | WT_Fast_FGF21 | Mouse liver |
| SA385469 | DBLiver_nP_3A | WT_Fast_FGF21 | Mouse liver |
| SA385470 | DBLiver_pP_3A | WT_Fast_FGF21 | Mouse liver |
| SA385471 | DBLiver_nP_3C | WT_Fast_FGF21 | Mouse liver |
| SA385472 | DBLiver_pP_3C | WT_Fast_FGF21 | Mouse liver |
| SA385473 | DBLiver_nP_3B | WT_Fast_FGF21 | Mouse liver |
| SA385474 | DBLiver_nP_2D | WT_Fast_Refeed | Mouse liver |
| SA385475 | DBLiver_nP_2C | WT_Fast_Refeed | Mouse liver |
| SA385476 | DBLiver_nP_2B | WT_Fast_Refeed | Mouse liver |
| SA385477 | DBLiver_pP_2C | WT_Fast_Refeed | Mouse liver |
| SA385478 | DBLiver_pP_2B | WT_Fast_Refeed | Mouse liver |
| SA385479 | DBLiver_pP_2D | WT_Fast_Refeed | Mouse liver |
| SA385480 | DBLiver_pP_1A | WT_Fast | Mouse liver |
| SA385481 | DBLiver_nP_2A | WT_Fast | Mouse liver |
| SA385482 | DBLiver_nP_1B | WT_Fast | Mouse liver |
| SA385483 | DBLiver_pP_1B | WT_Fast | Mouse liver |
| SA385484 | DBLiver_pP_2A | WT_Fast | Mouse liver |
| SA385485 | DBLiver_nP_1A | WT_Fast | Mouse liver |
| Showing results 1 to 34 of 34 |
Collection:
| Collection ID: | CO003616 |
| Collection Summary: | All mouse studies were approved by the Institutional Care and Use Committee at Washington University in Saint Louis. To perform infusion studies, a catheter (Instech, C20PU-MJV1301) was placed in the right jugular vein and connected to a vascular access button (Instech, VABM1B/25) implanted subcutaneously in the back of the mice. All surgeries were performed at the Hope Center for Neurological Diseases, Washington University. Mice were allowed to recover from surgery for at least one week before tracer infusion. U13C-Glucose (CIL, CLM-1396-PK) was fresh prepared in saline at a concentration of 200 mM. The mice were weighed to calculate the tracer infusion rate. To begin infusion, the vascular access button of individual mice was connected to the infusion line with a swivel (Instech, SMCLA), tether (Instech, KVABM1T/25), and infusion pump (CHEMYX, Fusion 100T). The infusion line was prefilled with 200 mM U13C-Glucose. Prime infusion was initiated at 1 ul/min/g for 2 minutes to clear the catheter locking solution, followed by continued infusion at 0.1 ul/min/g for 2 hours. Following completion of the glucose infusion, mice were anesthetized and blood was collected by cardiac puncture. Tissues were subsequently collected as quickly as possible (in 10 min or less) following euthanasia and snap frozen in liquid nitrogen. Tissues were stored at −80°C until processing for LC/MS analysis. |
| Sample Type: | Liver |
Treatment:
| Treatment ID: | TR003632 |
| Treatment Summary: | Mice are treated with or without FGF21, mice were either 16h-fasted or 14h-fasted plus 2h-refed |
Sample Preparation:
| Sampleprep ID: | SP003630 |
| Sampleprep Summary: | The liver tissue was mixed with ice-cold methanol:acetonitrile:water (2:2:1), and subjected to two cycles of 7m/s (30 s/cycle) using an Omni Bead Ruptor Elute Homogenizer. For every 1 mg of tissue wet weight, 40 uL of extraction solvent was added. Samples were then incubated at -20°C for 1 h to precipitate protein. Tissue extracts were centrifuged at 20,000 g and 4°C for 10 min, and the supernatant was transferred into LC/MS vials. |
Combined analysis:
| Analysis ID | AN005735 | AN005736 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Thermo Scientific QExactive Plus Mass Spectrometer | Thermo Scientific QExactive Plus Mass Spectrometer |
| Column | HILICON iHILIC-(P)-Classic column (100 x 2.1 mm, 5 um) | HILICON iHILIC-(P)-Classic column (100 x 2.1 mm, 5 um) |
| MS Type | Other | Other |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Plus Orbitrap | Thermo Q Exactive Plus Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Raw Area | Raw Area |
Chromatography:
| Chromatography ID: | CH004354 |
| Instrument Name: | Thermo Scientific QExactive Plus Mass Spectrometer |
| Column Name: | HILICON iHILIC-(P)-Classic column (100 x 2.1 mm, 5 um) |
| Column Temperature: | 40°C |
| Flow Gradient: | linear gradient; 0 – 1min, 90% B; 12min, 35% B; 12.5 – 14.5min, 25% B; 15min, 90% B |
| Flow Rate: | 0.25 mL/minute |
| Solvent A: | 95% Water/5% Acetonitrile; 20 mM ammonium bicarbonate, 2.5 uM medronic acid, 0.1% ammonium hydroxide |
| Solvent B: | 95% Acetonitrile/5% Water |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS005458 |
| Analysis ID: | AN005735 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | Other |
| MS Comments: | LC/MS data were processed and analyzed with the open-source Skyline software [Please cite: 10.1021/acs.jproteome.9b00640] Natural-abundance correction of 13C was performed with AccuCor [Please cite: 10.1021/acs.analchem.7b00396]. |
| Ion Mode: | POSITIVE |
| MS ID: | MS005459 |
| Analysis ID: | AN005736 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | Other |
| MS Comments: | LC/MS data were processed and analyzed with the open-source Skyline software [Please cite: 10.1021/acs.jproteome.9b00640] Natural-abundance correction of 13C was performed with AccuCor [Please cite: 10.1021/acs.analchem.7b00396]. |
| Ion Mode: | NEGATIVE |
