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.

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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 IDST003913
Study TitleAltered Metabolomics and Inflammatory Transcriptomics in Human Bone Marrow Adipocytes After Acute High Calorie Diet and Acute Fasting
Study TypeClinical Research
Study SummaryExpansion 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
DepartmentCenter for Molecular Medicine
LaboratoryClifford Rosen
Last NameVary
First NameCalvin
Address81 Research Dr. Scarborough ME
Emailcalvin.vary@mainehealth.org
Phone2073968148
Submit Date2025-04-16
Num Groups8; Fasting-Pre, Fasting-Post, HCD-Pre, HCD-Post for peripheral blood serum (PB) and bone marrow serum (BM)
Total Subjectsn = 4 for each dietary phase (HCD and fasting) and timepoint (Pre and Post)
Study CommentsSamples 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 AvailableYes
Raw Data File Type(s)mzXML, wiff
Analysis Type DetailLC-MS/MS(Dir. Inf.)
Release Date2025-05-26
Release Version1
Calvin Vary Calvin Vary
https://dx.doi.org/10.21228/M86R8C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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
SA430503BM-FastPost-D2aFasting Post_BM serum
SA430504BM-FastPost-B8bFasting Post_BM serum
SA430505BM-FastPost-E6bFasting Post_BM serum
SA430506BM-FastPost-E6aFasting Post_BM serum
SA430507BM-FastPost-D2bFasting Post_BM serum
SA430508BM-FastPost-B8aFasting Post_BM serum
SA430509BM-FastPost-C10bFasting Post_BM serum
SA430510BM-FastPost-C10aFasting Post_BM serum
SA430535PB-FastPost-B8aFasting Post_PB serum
SA430536PB-FastPost-B8bFasting Post_PB serum
SA430537PB-FastPost-C10aFasting Post_PB serum
SA430538PB-FastPost-C10bFasting Post_PB serum
SA430539PB-FastPost-D2aFasting Post_PB serum
SA430540PB-FastPost-D2bFasting Post_PB serum
SA430541PB-FastPost-E6aFasting Post_PB serum
SA430542PB-FastPost-E6bFasting Post_PB serum
SA430511BM-FastPre-B7bFasting Pre_BM serum
SA430512BM-FastPre-E5aFasting Pre_BM serum
SA430513BM-FastPre-D1bFasting Pre_BM serum
SA430514BM-FastPre-D1aFasting Pre_BM serum
SA430515BM-FastPre-C9bFasting Pre_BM serum
SA430516BM-FastPre-C9aFasting Pre_BM serum
SA430517BM-FastPre-B7aFasting Pre_BM serum
SA430518BM-FastPre-E5bFasting Pre_BM serum
SA430543PB-FastPre-E5bFasting Pre_PB serum
SA430544PB-FastPre-E5aFasting Pre_PB serum
SA430545PB-FastPre-D1bFasting Pre_PB serum
SA430546PB-FastPre-D1aFasting Pre_PB serum
SA430547PB-FastPre-C9bFasting Pre_PB serum
SA430548PB-FastPre-C9aFasting Pre_PB serum
SA430549PB-FastPre-B7aFasting Pre_PB serum
SA430550PB-FastPre-B7bFasting Pre_PB serum
SA430519BM-FastPost-D10aHigh Calorie Diet Post_BM serum
SA430520BM-FastPost-D10bHigh Calorie Diet Post_BM serum
SA430521BM-FastPost-C8aHigh Calorie Diet Post_BM serum
SA430522BM-FastPost-D6bHigh Calorie Diet Post_BM serum
SA430523BM-FastPost-D6aHigh Calorie Diet Post_BM serum
SA430524BM-FastPost-D4bHigh Calorie Diet Post_BM serum
SA430525BM-FastPost-D4aHigh Calorie Diet Post_BM serum
SA430526BM-FastPost-C8bHigh Calorie Diet Post_BM serum
SA430551PB-HCPost-C8aHigh Calorie Diet Post_PB serum
SA430552PB-HCPost-D10aHigh Calorie Diet Post_PB serum
SA430553PB-HCPost-D10bHigh Calorie Diet Post_PB serum
SA430554PB-HCPost-D4aHigh Calorie Diet Post_PB serum
SA430555PB-HCPost-D4bHigh Calorie Diet Post_PB serum
SA430556PB-HCPost-D6aHigh Calorie Diet Post_PB serum
SA430557PB-HCPost-D6bHigh Calorie Diet Post_PB serum
SA430558PB-HCPost-C8bHigh Calorie Diet Post_PB serum
SA430527BM-FastPre-D9aHigh Calorie Diet Pre_BM serum
SA430528BM-FastPre-D9bHigh Calorie Diet Pre_BM serum
SA430529BM-FastPre-D3bHigh Calorie Diet Pre_BM serum
SA430530BM-FastPre-D5bHigh Calorie Diet Pre_BM serum
SA430531BM-FastPre-D5aHigh Calorie Diet Pre_BM serum
SA430532BM-FastPre-D3aHigh Calorie Diet Pre_BM serum
SA430533BM-FastPre-C7bHigh Calorie Diet Pre_BM serum
SA430534BM-FastPre-C7aHigh Calorie Diet Pre_BM serum
SA430559PB-HCPre-D5bHigh Calorie Diet Pre_PB serum
SA430560PB-HCPre-D9aHigh Calorie Diet Pre_PB serum
SA430561PB-HCPre-D9bHigh Calorie Diet Pre_PB serum
SA430562PB-HCPre-D5aHigh Calorie Diet Pre_PB serum
SA430563PB-HCPre-D3aHigh Calorie Diet Pre_PB serum
SA430564PB-HCPre-C7bHigh Calorie Diet Pre_PB serum
SA430565PB-HCPre-C7aHigh Calorie Diet Pre_PB serum
SA430566PB-HCPre-D3bHigh Calorie Diet Pre_PB serum
SA430567Solvent-Last2Solvent
SA430568Solvent-Last8Solvent
SA430569Solvent-Last7Solvent
SA430570Solvent-Last6Solvent
SA430571Solvent-Last5Solvent
SA430572Solvent-Last4Solvent
SA430573Solvent-Last3Solvent
SA430574Solvent-First7Solvent
SA430575Solvent-Last1Solvent
SA430576Solvent-First8Solvent
SA430577Solvent-First6Solvent
SA430578Solvent-First5Solvent
SA430579Solvent-First4Solvent
SA430580Solvent-First3Solvent
SA430581Solvent-First1Solvent
SA430582Solvent-First-2Solvent
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
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