Summary of Study ST004085
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 PR002564. The data can be accessed directly via it's Project DOI: 10.21228/M8725N 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 | ST004085 |
| Study Title | Methionine restriction alters lipid beta-oxidation and levels of lipids associated with CVD risk |
| Study Summary | Given the observed improvements in metabolic parameters with short-term methionine restriction in obese mice consuming a sustained high-fat diet, we sought to understand the underlying systemic alterations by performing metabolomics of blood plasma. We observed decreased circulating phosphatidylcholines (PCs) and ceramide levels alongside an increase in circulating sphingomyelin levels. Reduced PC levels point towards alterations in mitochondrial energy metabolism, specifically lipid beta-oxidation, while altered ceramide and sphingomyelin levels may suggest a reduction in cardiac stress as high plasma ceramide levels have been linked with increased risk of cardiovascular disease (CVD). |
| Institute | Panome Bio |
| Last Name | Guzior |
| First Name | Douglas |
| Address | 4340 Duncan Ave, St. Louis, MO 63110 |
| douglas.guzior@panomebio.com | |
| Phone | (314) 632-6588 |
| Submit Date | 2025-03-26 |
| Num Groups | 4 |
| Total Subjects | 31 |
| Num Males | 31 |
| Study Comments | Part 3 of 3 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-08-25 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002564 |
| Project DOI: | doi: 10.21228/M8725N |
| Project Title: | Short-term restriction of dietary methionine counteracts metabolic dysfunction in obese mice fed a high fat diet |
| Project Summary: | Twenty-five-week-old male mice (n=31) with diet-induced obesity were divided into four groups to investigate the impact of methionine restriction on metabolic profiles within plasma, brown adipose tissue, and liver, aiming to determine if short-term dietary methionine restriction (MetR) could reverse the metabolic disruptions caused by a high-fat diet and to characterize the resulting alterations in protein and lipid signatures across these key metabolic tissues. The control group (n=8) was maintained on a high-fat diet (HFD, 60% kcal fat/0.86% methionine) for 15 weeks, while the intervention groups were fed a modified high-fat diet with significantly reduced methionine (HFD-MetR, 60% fat/0.12% methionine) for 3 days (MetR3, n=8), 5 days (MetR5, n=8), or 10 days (MetR10, n=7), with all mice fasted for 4 hours prior to the collection of biological samples for comprehensive metabolomic analysis. Our findings revealed that even short durations of HFD-MetR led to rapid and significant metabolic improvements, evidenced by reduced circulating triglyceride levels, blood glucose, and insulin within 10 days. Furthermore, significant changes in the secretion of adipokines and hepatokines were observed, alongside distinct alterations in the overall metabolomic profiles of plasma, brown adipose tissue, and liver. Proteomic analysis of perivascular adipose tissue (PVAT) complemented these findings by revealing enriched metabolic signatures. These data demonstrate that short-term dietary methionine restriction elicits rapid and substantial changes in the metabolome across multiple tissues in obese mice, highlighting its potential as a potent dietary intervention to reverse diet-induced metabolic dysfunction. |
| Institute: | Panome Bio |
| Last Name: | Guzior |
| First Name: | Douglas |
| Address: | 4340 Duncan Ave, St. Louis, MO 63110 |
| Email: | douglas.guzior@panomebio.com |
| Phone: | (314) 632-6588 |
Subject:
| Subject ID: | SU004231 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | C57BL/6J |
| Age Or Age Range: | 25 wk |
| Weight Or Weight Range: | >45g bodyweight at 25 w/o |
| Animal Light Cycle: | 12-hour light/12-hour dark photoperiod (0700 – 1900) |
| Animal Feed: | Research Diets D12492; Research Diets A14032002; Research Diets A14032001 |
| Animal Inclusion Criteria: | >45g bodyweight at 25 w/o |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | group | Sample source |
|---|---|---|---|
| SA473629 | blank1 | blank | blank |
| SA473613 | CF-6 | Control | Plasma |
| SA473614 | CF-5 | Control | Plasma |
| SA473615 | CF-8 | Control | Plasma |
| SA473616 | CF-7 | Control | Plasma |
| SA473617 | MR10-29 | MetR10 | Plasma |
| SA473618 | MR10-31 | MetR10 | Plasma |
| SA473619 | MR10-30 | MetR10 | Plasma |
| SA473620 | MR3-13 | MetR3 | Plasma |
| SA473621 | MR3-14 | MetR3 | Plasma |
| SA473622 | MR3-15 | MetR3 | Plasma |
| SA473623 | MR3-16 | MetR3 | Plasma |
| SA473624 | MR3-9 | MetR3 | Plasma |
| SA473625 | MR5-24 | MetR5 | Plasma |
| SA473626 | MR5-23 | MetR5 | Plasma |
| SA473627 | MR5-21 | MetR5 | Plasma |
| SA473628 | MR5-22 | MetR5 | Plasma |
| SA473630 | qc1 | qc | pooled_qc |
| SA473631 | qc2 | qc | pooled_qc |
| SA473632 | qc3 | qc | pooled_qc |
| Showing results 1 to 20 of 20 |
Collection:
| Collection ID: | CO004224 |
| Collection Summary: | Plasma samples were collected upon completion of the time course after fasting the mice for 4 h. |
| Sample Type: | Blood (plasma) |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR004240 |
| Treatment Summary: | Mice were weight-matched and divided into two groups fed either HFD-control (60% fat/0.86% methionine; Research Diets A14032002) or HFD-MetR (60% fat/0.12% methionine; Research Diets A14032001). The HFD-MetR group was split into 3 groups, where the HFD-MetR was administered for 3 days (MetR3, n=8), 5 days (MetR5, n=8), or 10 days (MetR10, n=7). HFD-MetR groups were compared to each other and the control group (HFD, n=8). |
| Treatment: | Dietary intervention and duration of altered diet |
| Treatment Route: | Diet |
| Treatment Dose: | Research Diets A14032002; Research Diets A14032001 |
| Treatment Dosevolume: | HFD-control (60% fat/0.86% methionine; Research Diets A14032002) or HFD-MetR (60% fat/0.12% methionine; Research Diets A14032001) |
| Treatment Doseduration: | 3-10 days |
| Treatment Vehicle: | Food |
| Animal Fasting: | 4h prior to sample collection |
Sample Preparation:
| Sampleprep ID: | SP004237 |
| Sampleprep Summary: | A 50 µL aliquot was transferred onto a solid phase extraction (SPE) system and 10 µL was taken from each sample to form the pooled quality control sample. 200 µL of 1:1 acetonitrile:methanol was added to each well and shaken for 1 min at room temperature at 360 rpm, followed by a 10 min incubation. Next, 150 µL of 2:2:1 methanol:acetonitrile:water was added to each well and taken again for 10 min. Polar metabolites were then eluted into the 96-well collection plate by using the positive pressure manifold. This is repeated with 100 µL of 2:2:1 methanol:acetonitrile:water into the same collection plate. Polar eluates were then covered and stored at -80°C until LC/MS analysis. The SPE plates from the polar metabolite extraction were then washed twice with 500 µL 1:1 methyl tert-butyl ether:methanol to elute non-polar metabolites into a new collection plate using a positive pressure manifold. The combined eluates were dried under a stream of nitrogen at room temperature and reconstituted with 200 µL 1:1 isopropanol:methanol and stored at -80°C prior to LC/MS analysis. |
| Processing Storage Conditions: | -80℃ |
| Extract Storage: | -80℃ |
| Sample Resuspension: | 2:2:1 methanol:acetonitrile:water |
Chromatography:
| Chromatography ID: | CH005142 |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | HILICON iHILIC (P)-Classic (100 x 2.1mm, 5um) |
| Column Temperature: | 45 |
| Flow Gradient: | 0-1 min: 90% B, 1-12 min: 90-35% B, 12-12.5 min: 35-20% B, 12.5 min-14.5 min: 20% B |
| Flow Rate: | 250 µL/min |
| Solvent A: | 95% water/5% acetonitrile; 20mM ammonium bicarbonate; 0.1% ammonium hydroxide; 2.5 µM medronic acid |
| Solvent B: | 95% water/5% acetonitrile |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH005143 |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) |
| Column Temperature: | 45 |
| Flow Gradient: | 0-2 min: 30% B, 2-17 min: 30-75% B, 17-20 min: 75-85% B, 20-23 min: 85-100% B, 23-26 min: 100% B, 26-27 min: 100-30% B |
| Flow Rate: | 400 µL/min |
| Solvent A: | 50% water/30% acetonitrile/20% isopropanol; 10 mM ammonium formate; 5 µM InfinityLab Deactivator Additive (Agilent) |
| Solvent B: | 90% isopropanol/10% acetonitrile; 10 mM ammonium formate; 0.1% formic acid; 2.5 mM medronic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN006769 |
| Analysis Type: | MS |
| Chromatography ID: | CH005142 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST004085_AN006769_Results.txt |
| Units: | log2-transformed normalized relative abundance |
| Analysis ID: | AN006770 |
| Analysis Type: | MS |
| Chromatography ID: | CH005142 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST004085_AN006770_Results.txt |
| Units: | log2-transformed normalized relative abundance |
| Analysis ID: | AN006771 |
| Analysis Type: | MS |
| Chromatography ID: | CH005143 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST004085_AN006771_Results.txt |
| Units: | log2-transformed normalized relative abundance |
| Analysis ID: | AN006772 |
| Analysis Type: | MS |
| Chromatography ID: | CH005143 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST004085_AN006772_Results.txt |
| Units: | log2-transformed normalized relative abundance |
