Summary of Study ST003426
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 PR002118. The data can be accessed directly via it's Project DOI: 10.21228/M8V53H 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 | ST003426 |
| Study Title | Metabolomic and transcriptomic remodeling of bone marrow myeloid cells in response to maternal obesity |
| Study Summary | Maternal obesity puts the offspring at high risk of developing obesity and cardio-metabolic diseases in adulthood. Here, using a mouse model of maternal high-fat diet-induced obesity, we show that whole body fat content of the Off-HFD increases significantly from very early age when compared to the Off-RD. We have previously shown significant metabolic and immune perturbations in the bone marrow of newly weaned offspring of obese mothers. Therefore, we hypothesized that lipid metabolism is altered in the bone marrow Off-HFD in newly weaned offspring of obese mothers when compared to the Off-RD. To test this hypothesis, we investigated the lipidomic profile of bone marrow cells collected from three-week-old offspring of regular and high fat diet-fed mothers. Diacylgycerols (DAGs), triacylglycerols (TAGs), sphingolipids and phospholipids, including plasmalogen, and lysophospholipids were remarkably different between the groups, independent of fetal sex. Levels of cholesteryl esters were significantly decreased in offspring of obese mothers, suggesting reduced delivery of cholesterol to bone marrow cells. This was accompanied by age-dependent progression of mitochondrial dysfunction in bone marrow cells. We subsequently isolated CD11b+ myeloid cells from three-week-old mice and conducted metabolomics, lipidomics, and transcriptomics analyses. The lipidomic profiles of these bone marrow myeloid cells were largely similar to that seen in bone marrow cells and included increases in DAGs and phospholipids alongside decreased TAGs, except for long-chain TAGs, which were significantly increased. Our data also revealed significant sex-dependent changes in amino acids and metabolites related to energy metabolism. Transcriptomic analysis revealed altered expression of genes related to major immune pathways including macrophage alternative activation, B-cell receptor signaling, TGF signaling, and communication between the innate and adaptive immune systems. All told, this study revealed lipidomic, metabolomic, and gene expression abnormalities in bone marrow cells broadly, and in bone marrow myeloid cells particularly, in the newly-weaned offspring of obese mothers, which might at least partially explain the progression of metabolic and cardiovascular diseases in their adulthood. |
| Institute | Oregon Health and Science University |
| Laboratory | Maloyan Laboratory |
| Last Name | Maloyan |
| First Name | Alina |
| Address | 3181 S.W. Sam Jackson Park Road, Portland, Oregon, 97239-3098, USA |
| maloyan@ohsu.edu | |
| Phone | 513-238-3783 |
| Submit Date | 2024-08-19 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-08-19 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002118 |
| Project DOI: | doi: 10.21228/M8V53H |
| Project Title: | Metabolomic and transcriptomic remodeling of bone marrow myeloid cells in response to maternal obesity |
| Project Summary: | Maternal obesity puts the offspring at high risk of developing obesity and cardio-metabolic diseases in adulthood. Here, using a mouse model of maternal high-fat diet-induced obesity, we show that whole body fat content of the Off-HFD increases significantly from very early age when compared to the Off-RD. We have previously shown significant metabolic and immune perturbations in the bone marrow of newly weaned offspring of obese mothers. Therefore, we hypothesized that lipid metabolism is altered in the bone marrow Off-HFD in newly weaned offspring of obese mothers when compared to the Off-RD. To test this hypothesis, we investigated the lipidomic profile of bone marrow cells collected from three-week-old offspring of regular and high fat diet-fed mothers. Diacylgycerols (DAGs), triacylglycerols (TAGs), sphingolipids and phospholipids, including plasmalogen, and lysophospholipids were remarkably different between the groups, independent of fetal sex. Levels of cholesteryl esters were significantly decreased in offspring of obese mothers, suggesting reduced delivery of cholesterol to bone marrow cells. This was accompanied by age-dependent progression of mitochondrial dysfunction in bone marrow cells. We subsequently isolated CD11b+ myeloid cells from three-week-old mice and conducted metabolomics, lipidomics, and transcriptomics analyses. The lipidomic profiles of these bone marrow myeloid cells were largely similar to that seen in bone marrow cells and included increases in DAGs and phospholipids alongside decreased TAGs, except for long-chain TAGs, which were significantly increased. Our data also revealed significant sex-dependent changes in amino acids and metabolites related to energy metabolism. Transcriptomic analysis revealed altered expression of genes related to major immune pathways including macrophage alternative activation, B-cell receptor signaling, TGF signaling, and communication between the innate and adaptive immune systems. All told, this study revealed lipidomic, metabolomic, and gene expression abnormalities in bone marrow cells broadly, and in bone marrow myeloid cells particularly, in the newly-weaned offspring of obese mothers, which might at least partially explain the progression of metabolic and cardiovascular diseases in their adulthood. |
| Institute: | Oregon Health and Science University |
| Department: | Knight Cardiovascular Institute |
| Laboratory: | Maloyan Laboratory |
| Last Name: | Maloyan |
| First Name: | Alina |
| Address: | 3181 S.W. Sam Jackson Park Road, Portland, Oregon, 97239-3098, USA |
| Email: | maloyan@ohsu.edu |
| Phone: | 513-238-3783 |
Subject:
| Subject ID: | SU003553 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Age Or Age Range: | 3 week old |
| Gender: | Male and female |
| Animal Housing: | regular |
| Animal Feed: | Fed by a regular or high fat diet |
| Animal Water: | ad libitum |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Offspring group | Sex |
|---|---|---|---|
| SA377689 | Maloyan_Asth_FOH3_l_21 | Offspring of High-Fat-Diet | Female |
| SA377690 | Maloyan_Asth_FOH1_l_19 | Offspring of High-Fat-Diet | Female |
| SA377691 | Maloyan_Asth_FOH2_l_20 | Offspring of High-Fat-Diet | Female |
| SA377692 | Maloyan_Asth_FOH6_l_24 | Offspring of High-Fat-Diet | Female |
| SA377693 | Maloyan_Asth_FOH5_l_23 | Offspring of High-Fat-Diet | Female |
| SA377694 | Maloyan_Asth_FOH4_l_22 | Offspring of High-Fat-Diet | Female |
| SA377695 | Maloyan_Asth_MOH6_l_12 | Offspring of High-Fat-Diet | Male |
| SA377696 | Maloyan_Asth_MOH5_l_11 | Offspring of High-Fat-Diet | Male |
| SA377697 | Maloyan_Asth_MOH3_l_09 | Offspring of High-Fat-Diet | Male |
| SA377698 | Maloyan_Asth_MOH4_l_10 | Offspring of High-Fat-Diet | Male |
| SA377699 | Maloyan_Asth_MOH1_l_07 | Offspring of High-Fat-Diet | Male |
| SA377700 | Maloyan_Asth_MOH2_l_08 | Offspring of High-Fat-Diet | Male |
| SA377701 | Maloyan_Asth_FOR6_l_18 | Offspring of Regular Diet | Female |
| SA377702 | Maloyan_Asth_FOR5_l_17 | Offspring of Regular Diet | Female |
| SA377703 | Maloyan_Asth_FOR1_l_13 | Offspring of Regular Diet | Female |
| SA377704 | Maloyan_Asth_FOR4_l_16 | Offspring of Regular Diet | Female |
| SA377705 | Maloyan_Asth_FOR3_l_15 | Offspring of Regular Diet | Female |
| SA377706 | Maloyan_Asth_FOR2_l_14 | Offspring of Regular Diet | Female |
| SA377707 | Maloyan_Asth_MOR1_l_01 | Offspring of Regular Diet | Male |
| SA377708 | Maloyan_Asth_MOR2_l_02 | Offspring of Regular Diet | Male |
| SA377709 | Maloyan_Asth_MOR3_l_03 | Offspring of Regular Diet | Male |
| SA377710 | Maloyan_Asth_MOR4_l_04 | Offspring of Regular Diet | Male |
| SA377711 | Maloyan_Asth_MOR5_l_05 | Offspring of Regular Diet | Male |
| SA377712 | Maloyan_Asth_MOR6_l_06 | Offspring of Regular Diet | Male |
| Showing results 1 to 24 of 24 |
Collection:
| Collection ID: | CO003546 |
| Collection Summary: | Bone marrow cells were isolated as previously reported (20). Briefly, femurs were flushed using a 25G5/8 needle with medium containing RPMI1640 + 2% FBS + 10 units/ml heparin + penicillin and streptomycin. Bits of bone were removed using a sterile 4 mm nylon cell strainer (Falcon 352340). Cells were dissolved in 50 ml medium and centrifuged at 2000 rpm (900 x g) for ten minutes at 4 °C. The resultant cell pellets were washed twice with 50 ml of serum-free RPMI (RPMI1640 + 20 mM Hepes + penicillin and streptomycin, adjusted to pH 7.4 before filtering), centrifuged at 2000 rpm at 4 °C for five minutes, and finally resuspended in 25 ml of serum-free RPMI. The obtained bone marrow cells were enriched for cells expressing CD11b using anti-CD11b magnetic beads (STEM CELL Technologies, Vancouver, BC), applied according to the manufacturer’s instructions. Isolated CD11b+ cells were sent for metabolomic, lipidomic, and transcriptomic analyses. |
| Collection Protocol Filename: | Lipidomics_and_metabolomics.pdf |
| Sample Type: | Bone marrow |
Treatment:
| Treatment ID: | TR003562 |
| Treatment Summary: | To induce maternal obesity, high-fat diet (Teklad Cat#TD.06415) or its control, a regular diet (RD, PicoLab® Laboratory Rodent Diet Cat # 5LOD) was given to virgin female FVB/NJ mice from the six-weeks of age and throughout the entire study. After eight weeks of dietary intervention, RD- and HFD-fed female mice were bred to an age-matched RD-fed male. At weaning, male and female offspring from each mother were randomly selected for the study. The offspring were fed a regular diet only starting from weaning and throughout their life. |
Sample Preparation:
| Sampleprep ID: | SP003560 |
| Sampleprep Summary: | Lipids and metabolites were extracted from cells using MPLEx (Metabolite, Protein, Lipid Extraction). First, 1 mL cold (-20 °C) chloroform:methanol working mix (prepared 2:1, v/v) was added into a chloroform-compatible 2 mL Sorenson MulTI™ SafeSeal™ microcentrifuge tube (Sorenson Bioscience, Salt Lake City, UT) inside an ice-block. The sample and cold water were then added to make a final ratio of 8:4:3 chloroform:methanol:water/sample, vortexed, allowed to incubate in the ice block for 15 mins with 2000 rpm shaking, and finally sonicated in an ice water bath sonicator. Afterwards, the samples were centrifuged at 12,000 x g for 10 mins to separate the polar and non-polar phases and the protein interlayer. The upper polar phase and a portion of the lower non-polar phase were allotted to metabolite samples, with the remaining lower non-polar phase used for lipid samples. The whole process was repeated once on the protein interlayer to ensure complete removal of metabolites and lipids. The protein was then washed with 500 µl of cold 100% methanol and centrifuged for five minutes to pellet the protein, and the wash layer was added to the metabolites vial. Metabolite and lipid samples were dried in a speed vac, and 500 µl 2:1 (v:v) cold chloroform:methanol was added to the lipids, which were ultimately stored along with the dry metabolites at -20 °C until analysis. |
| Sampleprep Protocol Filename: | Lipidomics_and_metabolomics.pdf |
Chromatography:
| Chromatography ID: | CH004275 |
| Instrument Name: | Waters Acquity H-Class |
| Column Name: | Waters ACQUITY UPLC CSH C18 (150 x 3mm, 1.7um) |
| Column Temperature: | 42 |
| Flow Gradient: | Time (min), %B: 0, 40; 2, 50; 3, 60; 12, 70; 15, 75; 17, 78; 19, 85; 22, 92; 25, 99; 34, 99; and 34.5, 40 |
| Flow Rate: | 250 uL/min |
| Solvent A: | 40% acetonitrile/60% water; 10 mM ammonium acetate |
| Solvent B: | 10% acetonitrile/90% isopropanol; 10 mM ammonium acetate |
| Chromatography Type: | Other |
Analysis:
| Analysis ID: | AN005625 |
| Analysis Type: | MS |
| Analysis Protocol File: | Lipidomics_and_metabolomics.pdf |
| Chromatography ID: | CH004275 |
| Num Factors: | 4 |
| Num Metabolites: | 106 |
| Units: | median normalized log 2 transformed peak area |
| Analysis ID: | AN005626 |
| Analysis Type: | MS |
| Analysis Protocol File: | Lipidomics_and_metabolomics.pdf |
| Chromatography ID: | CH004275 |
| Num Factors: | 4 |
| Num Metabolites: | 59 |
| Units: | median normalized log 2 transformed peak areas |
