Summary of Study ST003913
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 PR002448. The data can be accessed directly via it's Project DOI: 10.21228/M86R8C 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 | ST003913 |
| Study Title | Altered Metabolomics and Inflammatory Transcriptomics in Human Bone Marrow Adipocytes After Acute High Calorie Diet and Acute Fasting |
| Study Type | Clinical Research |
| Study Summary | Expansion of bone marrow (BM) adipocytes has been linked to nutritional pressures, suggesting that BM is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here we investigated BM metabolism in response to acute overnutrition (high calorie diet; HCD) and calorie deprivation (fasting). Participants underwent a 10-day HCD followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting. BM adipocytes and sera were collected before and after each dietary intervention. Using comprehensive and integrated analyses, we characterized nutritional influences on BM adiposity. BM adipocytes after HCD showed an upregulation of FOXP3 (p < 0.0001), the transcription factor that controls the development of Tregs, which are critical in reducing inflammatory immune responses. After fasting, BM adipocytes had an upregulation of inflammatory genes (CP, CFH, and IGFBP3) (p < 0.0001). Proteomic analysis after HCD showed that BM serum had an upregulation of proteins related to an inflammatory/complement pathway (PROC, RBP4, and CFI). After fasting, in BM serum there was a significant downregulation of inflammatory/complement pathway proteins (C1QC and RBP4). Despite both interventions causing BM adipose tissue expansion, the mechanism for adipogenesis appears to be dependent on nutrient availability. After HCD, lipid-mediated signaling and lipid storage and lipid droplet biogenesis were significantly downregulated (p < 0.0001). In contrast, after fasting lipid-mediated signaling and lipid storage and lipid droplet biogenesis were significantly upregulated (p < 0.0001). Overall, our results demonstrate key differences in inflammatory response and lipid metabolism between HCD and fasting, despite a nearly identical BM adipose phenotype. Further analyses are needed to understand the effects nutritional pressures have on BM adipogenesis and immune responses. |
| Institute | MaineHealth Institute for Research |
| Department | Center for Molecular Medicine |
| Laboratory | Clifford Rosen |
| Last Name | Vary |
| First Name | Calvin |
| Address | 81 Research Dr. Scarborough ME |
| calvin.vary@mainehealth.org | |
| Phone | 2073968148 |
| Submit Date | 2025-04-16 |
| Num Groups | 8; Fasting-Pre, Fasting-Post, HCD-Pre, HCD-Post for peripheral blood serum (PB) and bone marrow serum (BM) |
| Total Subjects | n = 4 for each dietary phase (HCD and fasting) and timepoint (Pre and Post) |
| Study Comments | Samples from four participants were used from a total of 10 women and 13 men. The sex of these four participants is unknown. Only these samples were used because we had enough peripheral blood and bone marrow sera from each of these participants to perform paired lipidomic analyses on the High Calorie-Post and -Pre as well as the Fasting-Post and -Pre. This way direct comparisons can be made between the peripheral blood and bone marrow sera and the dietary phases. |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML, wiff |
| Analysis Type Detail | LC-MS/MS(Dir. Inf.) |
| Release Date | 2025-05-26 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002448 |
| Project DOI: | doi: 10.21228/M86R8C |
| Project Title: | Altered Metabolomics and Inflammatory Transcriptomics in Human Bone Marrow Adipocytes After Acute High Calorie Diet and Acute Fasting |
| Project Type: | Clinical Research |
| Project Summary: | Expansion of bone marrow (BM) adipocytes has been linked to nutritional pressures, suggesting that BM is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here we investigated BM metabolism in response to acute overnutrition (high calorie diet; HCD) and calorie deprivation (fasting). Participants underwent a 10-day HCD followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting. BM adipocytes and sera were collected before and after each dietary intervention. Using comprehensive and integrated analyses, we characterized nutritional influences on BM adiposity. BM adipocytes after HCD showed an upregulation of FOXP3 (p < 0.0001), the transcription factor that controls the development of Tregs, which are critical in reducing inflammatory immune responses. After fasting, BM adipocytes had an upregulation of inflammatory genes (CP, CFH, and IGFBP3) (p < 0.0001). Proteomic analysis after HCD showed that BM serum had an upregulation of proteins related to an inflammatory/complement pathway (PROC, RBP4, and CFI). After fasting, in BM serum there was a significant downregulation of inflammatory/complement pathway proteins (C1QC and RBP4). Despite both interventions causing BM adipose tissue expansion, the mechanism for adipogenesis appears to be dependent on nutrient availability. After HCD, lipid-mediated signaling and lipid storage and lipid droplet biogenesis were significantly downregulated (p < 0.0001). In contrast, after fasting lipid-mediated signaling and lipid storage and lipid droplet biogenesis were significantly upregulated (p < 0.0001). Overall, our results demonstrate key differences in inflammatory response and lipid metabolism between HCD and fasting, despite a nearly identical BM adipose phenotype. Further analyses are needed to understand the effects nutritional pressures have on BM adipogenesis and immune responses. |
| Institute: | MaineHealth Institute for Research |
| Department: | Center for Molecular Medicine |
| Laboratory: | Clifford Rosen |
| Last Name: | Vary |
| First Name: | Calvin |
| Address: | 81 Research Dr. Scarborough ME |
| Email: | calvin.vary@mainehealth.org |
| Phone: | 2073968148 |
Subject:
| Subject ID: | SU004048 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Age Or Age Range: | 22–44 years |
| Weight Or Weight Range: | BMI: 23.3–27.9 |
| Gender: | Pooled |
| Human Lifestyle Factors: | No subject had a history of diabetes mellitus or a history of an eating disorder. All women were premenopausal and had a history of regular menstrual cycles, and none had used exogenous estrogen within 3 months |
| Human Medications: | None of the participants were taking chronic medications |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA430503 | BM-FastPost-D2a | Fasting Post_BM serum |
| SA430504 | BM-FastPost-B8b | Fasting Post_BM serum |
| SA430505 | BM-FastPost-E6b | Fasting Post_BM serum |
| SA430506 | BM-FastPost-E6a | Fasting Post_BM serum |
| SA430507 | BM-FastPost-D2b | Fasting Post_BM serum |
| SA430508 | BM-FastPost-B8a | Fasting Post_BM serum |
| SA430509 | BM-FastPost-C10b | Fasting Post_BM serum |
| SA430510 | BM-FastPost-C10a | Fasting Post_BM serum |
| SA430535 | PB-FastPost-B8a | Fasting Post_PB serum |
| SA430536 | PB-FastPost-B8b | Fasting Post_PB serum |
| SA430537 | PB-FastPost-C10a | Fasting Post_PB serum |
| SA430538 | PB-FastPost-C10b | Fasting Post_PB serum |
| SA430539 | PB-FastPost-D2a | Fasting Post_PB serum |
| SA430540 | PB-FastPost-D2b | Fasting Post_PB serum |
| SA430541 | PB-FastPost-E6a | Fasting Post_PB serum |
| SA430542 | PB-FastPost-E6b | Fasting Post_PB serum |
| SA430511 | BM-FastPre-B7b | Fasting Pre_BM serum |
| SA430512 | BM-FastPre-E5a | Fasting Pre_BM serum |
| SA430513 | BM-FastPre-D1b | Fasting Pre_BM serum |
| SA430514 | BM-FastPre-D1a | Fasting Pre_BM serum |
| SA430515 | BM-FastPre-C9b | Fasting Pre_BM serum |
| SA430516 | BM-FastPre-C9a | Fasting Pre_BM serum |
| SA430517 | BM-FastPre-B7a | Fasting Pre_BM serum |
| SA430518 | BM-FastPre-E5b | Fasting Pre_BM serum |
| SA430543 | PB-FastPre-E5b | Fasting Pre_PB serum |
| SA430544 | PB-FastPre-E5a | Fasting Pre_PB serum |
| SA430545 | PB-FastPre-D1b | Fasting Pre_PB serum |
| SA430546 | PB-FastPre-D1a | Fasting Pre_PB serum |
| SA430547 | PB-FastPre-C9b | Fasting Pre_PB serum |
| SA430548 | PB-FastPre-C9a | Fasting Pre_PB serum |
| SA430549 | PB-FastPre-B7a | Fasting Pre_PB serum |
| SA430550 | PB-FastPre-B7b | Fasting Pre_PB serum |
| SA430519 | BM-FastPost-D10a | High Calorie Diet Post_BM serum |
| SA430520 | BM-FastPost-D10b | High Calorie Diet Post_BM serum |
| SA430521 | BM-FastPost-C8a | High Calorie Diet Post_BM serum |
| SA430522 | BM-FastPost-D6b | High Calorie Diet Post_BM serum |
| SA430523 | BM-FastPost-D6a | High Calorie Diet Post_BM serum |
| SA430524 | BM-FastPost-D4b | High Calorie Diet Post_BM serum |
| SA430525 | BM-FastPost-D4a | High Calorie Diet Post_BM serum |
| SA430526 | BM-FastPost-C8b | High Calorie Diet Post_BM serum |
| SA430551 | PB-HCPost-C8a | High Calorie Diet Post_PB serum |
| SA430552 | PB-HCPost-D10a | High Calorie Diet Post_PB serum |
| SA430553 | PB-HCPost-D10b | High Calorie Diet Post_PB serum |
| SA430554 | PB-HCPost-D4a | High Calorie Diet Post_PB serum |
| SA430555 | PB-HCPost-D4b | High Calorie Diet Post_PB serum |
| SA430556 | PB-HCPost-D6a | High Calorie Diet Post_PB serum |
| SA430557 | PB-HCPost-D6b | High Calorie Diet Post_PB serum |
| SA430558 | PB-HCPost-C8b | High Calorie Diet Post_PB serum |
| SA430527 | BM-FastPre-D9a | High Calorie Diet Pre_BM serum |
| SA430528 | BM-FastPre-D9b | High Calorie Diet Pre_BM serum |
| SA430529 | BM-FastPre-D3b | High Calorie Diet Pre_BM serum |
| SA430530 | BM-FastPre-D5b | High Calorie Diet Pre_BM serum |
| SA430531 | BM-FastPre-D5a | High Calorie Diet Pre_BM serum |
| SA430532 | BM-FastPre-D3a | High Calorie Diet Pre_BM serum |
| SA430533 | BM-FastPre-C7b | High Calorie Diet Pre_BM serum |
| SA430534 | BM-FastPre-C7a | High Calorie Diet Pre_BM serum |
| SA430559 | PB-HCPre-D5b | High Calorie Diet Pre_PB serum |
| SA430560 | PB-HCPre-D9a | High Calorie Diet Pre_PB serum |
| SA430561 | PB-HCPre-D9b | High Calorie Diet Pre_PB serum |
| SA430562 | PB-HCPre-D5a | High Calorie Diet Pre_PB serum |
| SA430563 | PB-HCPre-D3a | High Calorie Diet Pre_PB serum |
| SA430564 | PB-HCPre-C7b | High Calorie Diet Pre_PB serum |
| SA430565 | PB-HCPre-C7a | High Calorie Diet Pre_PB serum |
| SA430566 | PB-HCPre-D3b | High Calorie Diet Pre_PB serum |
| SA430567 | Solvent-Last2 | Solvent |
| SA430568 | Solvent-Last8 | Solvent |
| SA430569 | Solvent-Last7 | Solvent |
| SA430570 | Solvent-Last6 | Solvent |
| SA430571 | Solvent-Last5 | Solvent |
| SA430572 | Solvent-Last4 | Solvent |
| SA430573 | Solvent-Last3 | Solvent |
| SA430574 | Solvent-First7 | Solvent |
| SA430575 | Solvent-Last1 | Solvent |
| SA430576 | Solvent-First8 | Solvent |
| SA430577 | Solvent-First6 | Solvent |
| SA430578 | Solvent-First5 | Solvent |
| SA430579 | Solvent-First4 | Solvent |
| SA430580 | Solvent-First3 | Solvent |
| SA430581 | Solvent-First1 | Solvent |
| SA430582 | Solvent-First-2 | Solvent |
| Showing results 1 to 80 of 80 |
Collection:
| Collection ID: | CO004041 |
| Collection Summary: | Peripheral blood serum: On the first day of each dietary phase (baseline day) and the final high-calorie day and final fasting day, blood was drawn from each subject for laboratory studies (subjects were fasted before blood draws). Bone marrow sera: After the bone marrow aspiration, PBS 5 cc was added to the aspirate (also containing cells) and collected in the EDTA tube. Bone marrow aspirate was then spun at 377g for 8 minutes at 4°C. The remaining components were divided into 3 compartments: compartment 1, pellet, which contained the stromal vascular fraction; compartment 2, the fluid between the pellet and the top layer, which we called bone marrow serum because of its appearance; and compartment 3, the top layer of floated cells. |
| Sample Type: | Bone Marrow Serum and Blood Serum |
| Collection Frequency: | before (pre) and on the final day (post) of each dietary phase |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR004057 |
| Treatment Summary: | Other than the dietary interventions, participants did not receive any medical treatments. |
Sample Preparation:
| Sampleprep ID: | SP004054 |
| Sampleprep Summary: | 10 µL serum aliquots from the Pre and Post of each dietary phase (High calorie diet and fasting) were provided to the MHIR Proteomics and Lipidomics Core Facility for analysis. The individual samples were sub-divided into technical replicates, which were then averaged together. Lipid extracts were dissolved in methanol/dichloromethane for mass spectrometry (MS) analysis. Multiple precursor ion scanning workflow lipidomic analyses were conducted using a 4000 QTRAP mass spectrometer (Sciex, Framingham, MA) and downstream analyses, including t-tests and principal component analyses (PCAs), were completed utilizing MarkerView Software (Sciex). PCAs were performed with no weighting, Pareto scaling, and supervised data analysis. Lipids were analyzed using a global, lipid profiling acquisition technique (MPIS). Note; positive, negative and neutral loss loop are contained in the same instrument file. |
| Processing Storage Conditions: | -80℃ |
| Extract Storage: | -80℃ |
Chromatography:
| Chromatography ID: | CH004874 |
| Chromatography Summary: | NA |
| Instrument Name: | none |
| Column Name: | none |
| Column Temperature: | n/a |
| Flow Gradient: | n/a |
| Flow Rate: | n/a |
| Solvent A: | n/a |
| Solvent B: | n/a |
| Chromatography Type: | None (Direct infusion) |
Analysis:
| Analysis ID: | AN006425 |
| Laboratory Name: | Proteomics and Lipidomics Core |
| Analysis Type: | MS |
| Acquisition Date: | 9/2022 |
| Software Version: | Analyst 1.7.3 |
| Operator Name: | Calvin Vary |
| Detector Type: | ESI |
| Data Format: | wiff |
| Chromatography ID: | CH004874 |
| Num Factors: | 9 |
| Num Metabolites: | 1256 |
| Units: | intensity |
| Analysis ID: | AN006426 |
| Laboratory Name: | Proteomics and Lipidomics Core |
| Analysis Type: | MS |
| Acquisition Date: | 9/2022 |
| Software Version: | Analyst 1.7.3 |
| Operator Name: | Calvin Vary |
| Detector Type: | ESI |
| Data Format: | wiff |
| Chromatography ID: | CH004874 |
| Num Factors: | 9 |
| Num Metabolites: | 3270 |
| Units: | intensity |