Summary of Study ST004373

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 PR002771. The data can be accessed directly via it's Project DOI: 10.21228/M8GK03 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study ID	ST004373
Study Title	In C57BL/6J mice, weight loss in previously obese mice shifted the cortical bone metabolome
Study Summary	Obesity is linked to increased fracture risk. Despite the negative effects of weight loss on the skeleton, patients with obesity are advised to lose weight via calorie restriction. Obesity and weight loss individually alter both whole-body and local metabolism. Little is known about changes to bone mass and metabolome following calorie restriction in obese preclinical models. We hypothesized that caloric restriction would worsen bone quality in obese mice by shifting the cortical bone metabolome. To induce obesity, 8-week-old male and female C57BL/6J mice received 60% kCal high-fat diet for 12 weeks. From 20 to 30 weeks of age, mice either remained obese or lost weight through 30% caloric restriction. Controls consumed 10% kCal low-fat diet. Compared to obesity, calorie restriction elicited more bone loss in both cortical and trabecular compartments. Weight loss also reduced bone formation. Both obesity and subsequent calorie restriction altered the cortical bone metabolome in a sex-dependent manner. Metabolic pathways altered with diet generally mapped to amino acid or fatty acid metabolism. In males, weight loss was associated with a downregulation of pathways related to tryptophan, tyrosine, ubiquinone, and fatty acids. In females, calorie restriction downregulated taurine and hypotaurine metabolism but upregulated pyrimidine metabolism, nicotinate and nicotinamide metabolism, and pantothenate and CoA biosynthesis. Our findings highlight the negative effects of obesity and subsequent caloric restriction on the skeleton. Despite improvements in components of systemic metabolism, caloric restriction in obese preclinical models did not restore bone morphology or the cortical metabolome to control conditions.
Institute	MaineHealth Institute for Research
Last Name	Chlebek
First Name	Carolyn
Address	81 Research Drive
Email	carolyn.chlebek@mainehealth.org
Phone	5085107184
Submit Date	2025-10-27
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2025-12-15
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR002771
Project DOI:	doi: 10.21228/M8GK03
Project Title:	In C57BL/6J mice, weight loss in previously obese mice shifted the cortical bone metabolome
Project Summary:	8-week-old male and female C57BL/6 J mice received 60 % kCal high-fat diet for 12 weeks. From 20 to 30 weeks of age, mice either remained obese or lost weight through 30 % caloric restriction. Controls consumed 10 % kCal low-fat diet. Mice were euthanized at 30 weeks of age, and cortical bone was obtained for metabolomic analyses. Metabolites were extracted and underwent LC-MS analysis using Waters I-Class Ultra-High Performance Liquid Chromatography coupled to a Waters Synapt-XS Q-IMS-TOF in positive mode.
Institute:	MaineHealth Institute for Research
Last Name:	Chlebek
First Name:	Carolyn
Address:	81 Research Drive
Email:	carolyn.chlebek@mainehealth.org
Phone:	5085107184

Subject:

Subject ID:	SU004532
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090
Age Or Age Range:	30 wks
Gender:	Male and female
Animal Light Cycle:	14 h light: 10 h dark
Species Group:	C57BL/6J

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Diet	Sex	Sample source
SA520097	20240712_PB-Rosen_01_317	Ctrl	Female	Cortical_Bone
SA520098	20240712_PB-Rosen_01_301	Ctrl	Female	Cortical_Bone
SA520099	20240712_PB-Rosen_01_302	Ctrl	Female	Cortical_Bone
SA520100	20240712_PB-Rosen_01_311	Ctrl	Female	Cortical_Bone
SA520101	20240712_PB-Rosen_01_313	Ctrl	Female	Cortical_Bone
SA520102	20240712_PB-Rosen_01_316	Ctrl	Female	Cortical_Bone
SA520103	20240712_PB-Rosen_01_315	Ctrl	Female	Cortical_Bone
SA520104	20240712_PB-Rosen_01_213	Ctrl	Male	Cortical_Bone
SA520105	20240712_PB-Rosen_01_218	Ctrl	Male	Cortical_Bone
SA520106	20240712_PB-Rosen_01_211	Ctrl	Male	Cortical_Bone
SA520107	20240712_PB-Rosen_01_207	Ctrl	Male	Cortical_Bone
SA520108	20240712_PB-Rosen_01_214	Ctrl	Male	Cortical_Bone
SA520109	20240712_PB-Rosen_01_202	Ctrl	Male	Cortical_Bone
SA520110	20240712_PB-Rosen_01_215	Ctrl	Male	Cortical_Bone
SA520111	20240712_PB-Rosen_01_217	Ctrl	Male	Cortical_Bone
SA520112	20240712_PB-Rosen_01_326	HFD-CR	Female	Cortical_Bone
SA520113	20240712_PB-Rosen_01_344	HFD-CR	Female	Cortical_Bone
SA520114	20240712_PB-Rosen_01_342	HFD-CR	Female	Cortical_Bone
SA520115	20240712_PB-Rosen_01_332	HFD-CR	Female	Cortical_Bone
SA520116	20240712_PB-Rosen_01_219	HFD-CR	Male	Cortical_Bone
SA520117	20240712_PB-Rosen_01_225	HFD-CR	Male	Cortical_Bone
SA520118	20240712_PB-Rosen_01_228	HFD-CR	Male	Cortical_Bone
SA520119	20240712_PB-Rosen_01_241	HFD-CR	Male	Cortical_Bone
SA520120	20240712_PB-Rosen_01_230	HFD-CR	Male	Cortical_Bone
SA520121	20240712_PB-Rosen_01_249	HFD-CR	Male	Cortical_Bone
SA520122	20240712_PB-Rosen_01_248	HFD-CR	Male	Cortical_Bone
SA520123	20240712_PB-Rosen_01_238	HFD-CR	Male	Cortical_Bone
SA520124	20240712_PB-Rosen_01_240	HFD-CR	Male	Cortical_Bone
SA520125	20240712_PB-Rosen_01_321	HFD	Female	Cortical_Bone
SA520126	20240712_PB-Rosen_01_333	HFD	Female	Cortical_Bone
SA520127	20240712_PB-Rosen_01_337	HFD	Female	Cortical_Bone
SA520128	20240712_PB-Rosen_01_352	HFD	Female	Cortical_Bone
SA520129	20240712_PB-Rosen_01_247	HFD	Male	Cortical_Bone
SA520130	20240712_PB-Rosen_01_252	HFD	Male	Cortical_Bone
SA520131	20240712_PB-Rosen_01_245	HFD	Male	Cortical_Bone
SA520132	20240712_PB-Rosen_01_242	HFD	Male	Cortical_Bone
SA520133	20240712_PB-Rosen_01_223	HFD	Male	Cortical_Bone
SA520134	20240712_PB-Rosen_01_232	HFD	Male	Cortical_Bone
SA520135	20240712_PB-Rosen_01_227	HFD	Male	Cortical_Bone
SA520136	20240712_PB-Rosen_01_221	HFD	Male	Cortical_Bone
SA520137	20240712_PB-Rosen_01_02_blank	NA - Blank	NA - Blank	NA
SA520138	20240712_PB-Rosen_01_03_blank	NA - Blank	NA - Blank	NA
SA520139	20240712_PB-Rosen_01_04_blank	NA - Blank	NA - Blank	NA
SA520140	20240712_PB-Rosen_01_05_blank	NA - Blank	NA - Blank	NA
SA520141	20240712_PB-Rosen_01_06_blank	NA - Blank	NA - Blank	NA
SA520142	20240712_PB-Rosen_01_07_blank	NA - Blank	NA - Blank	NA
SA520143	20240712_PB-Rosen_01_00_blank	NA - Blank	NA - Blank	NA
SA520144	20240712_PB-Rosen_01_01_blank	NA - Blank	NA - Blank	NA
SA520145	20240712_PB-Rosen_01_06_neat	NA - Neat	NA - Neat	NA
SA520146	20240712_PB-Rosen_01_05_neat	NA - Neat	NA - Neat	NA
SA520147	20240712_PB-Rosen_01_03_neat	NA - Neat	NA - Neat	NA
SA520148	20240712_PB-Rosen_01_02_neat	NA - Neat	NA - Neat	NA
SA520149	20240712_PB-Rosen_01_01_neat	NA - Neat	NA - Neat	NA
SA520150	20240712_PB-Rosen_01_00_neat	NA - Neat	NA - Neat	NA
SA520151	20240712_PB-Rosen_01_04_neat	NA - Neat	NA - Neat	NA
SA520152	20240712_PB-Rosen_01_P1	NA - Pooled samples	NA - Pooled samples	Cortical_Bone
SA520153	20240712_PB-Rosen_01_P2	NA - Pooled samples	NA - Pooled samples	Cortical_Bone
SA520154	20240712_PB-Rosen_01_P3	NA - Pooled samples	NA - Pooled samples	Cortical_Bone
SA520155	20240712_PB-Rosen_01_P4	NA - Pooled samples	NA - Pooled samples	Cortical_Bone
SA520156	20240712_PB-Rosen_01_P5	NA - Pooled samples	NA - Pooled samples	Cortical_Bone
SA520157	20240712_PB-Rosen_01_P6	NA - Pooled samples	NA - Pooled samples	Cortical_Bone

Showing results 1 to 61 of 61

Showing results 1 to 61 of 61

Collection:

Collection ID:	CO004525
Collection Summary:	At euthanasia, femurs were cleaned of soft tissues and periosteum. Bone marrow was removed via centrifugation from femurs in all animals. Trabecular bone was removed from the femur and the cortical shell flash frozen in liquid nitrogen.
Sample Type:	Bone

Treatment:

Treatment ID:	TR004541
Treatment Summary:	Male and female C57BL/6J mice aged 5 weeks (Jackson Laboratories, Bar Harbor, ME) were acclimated for three weeks prior to the experiment. All mouse procedures were performed under the approval of the Institutional Animal Care and Use Committee (IACUC) at the MaineHealth Institute for Research. Throughout the study, mice were housed in 14-hour light:10-hour dark cycles. At 8 weeks of age, the High Fat Feeding Phase was initiated. During the High Fat Feeding Phase, mice were housed in groups of two or three per cage. Cages were randomly assigned to receive a 60% high fat diet, containing 60% of calories from fat or a 10% kcal low fat diet, containing 10% of calories from fat (D12492i and D12450Ji, respectively; Research Diets Inc, New Brunswick, NJ). High fat diet was completely replaced every 2-3 days. Following obesity induction, obese mice were randomly assigned to remain on the high fat diet (HFD) or were assigned to the diet-induced weight loss (HFD-CR). At the conclusion of the High Fat Feeding Phase, all mice were single housed. HFD animals continued to receive 60 % high fat diet. HFD-CR mice received the low fat diet for 2 weeks (Stabilization Phase) and were then transitioned to a 30 % calorie-restricted diet for 8 weeks (Caloric Restriction Phase) (Fig. 1A). All mice were euthanized at the end of the Caloric Restriction Phase, at 30 weeks of age.

Treatment ID:

TR004541

Treatment Summary:

Male and female C57BL/6J mice aged 5 weeks (Jackson Laboratories, Bar Harbor, ME) were acclimated for three weeks prior to the experiment. All mouse procedures were performed under the approval of the Institutional Animal Care and Use Committee (IACUC) at the MaineHealth Institute for Research. Throughout the study, mice were housed in 14-hour light:10-hour dark cycles. At 8 weeks of age, the High Fat Feeding Phase was initiated. During the High Fat Feeding Phase, mice were housed in groups of two or three per cage. Cages were randomly assigned to receive a 60% high fat diet, containing 60% of calories from fat or a 10% kcal low fat diet, containing 10% of calories from fat (D12492i and D12450Ji, respectively; Research Diets Inc, New Brunswick, NJ). High fat diet was completely replaced every 2-3 days. Following obesity induction, obese mice were randomly assigned to remain on the high fat diet (HFD) or were assigned to the diet-induced weight loss (HFD-CR). At the conclusion of the High Fat Feeding Phase, all mice were single housed. HFD animals continued to receive 60 % high fat diet. HFD-CR mice received the low fat diet for 2 weeks (Stabilization Phase) and were then transitioned to a 30 % calorie-restricted diet for 8 weeks (Caloric Restriction Phase) (Fig. 1A). All mice were euthanized at the end of the Caloric Restriction Phase, at 30 weeks of age.

Sample Preparation:

Sampleprep ID:	SP004538
Sampleprep Summary:	Using a bead mill, bone was pulverized in a 70:30 methanol:acetone solution. Samples were centrifuged and supernatant containing metabolites was extracted. Supernatant was then dried in vacuum concentrator. Metabolites were then resuspended in 1:1 acetonitrile:water. All solvents used were high-performance liquid chromatography grade.

Combined analysis:

Analysis ID	AN007307
Chromatography ID	CH005548
MS ID	MS007001
Analysis type	MS
Chromatography type	HILIC
Chromatography system	Waters I-Class Ultra-High Performance Liquid Chromatography
Column	MicroSolv Diamond Hydride (150 x 2.1mm, 2.2 um, 120A)
MS Type	ESI
MS instrument type	QTOF
MS instrument name	Waters Synapt-XS
Ion Mode	POSITIVE
Units	arbitrary units

Chromatography:

Chromatography ID:	CH005548
Instrument Name:	Waters I-Class Ultra-High Performance Liquid Chromatography
Column Name:	MicroSolv Diamond Hydride (150 x 2.1mm, 2.2 um, 120A)
Column Temperature:	50
Flow Gradient:	Linear: Time(min); Flow Rate; %A; %B. Initial; 0.4; 10; 90. 2; 0.4; 10; 90. 8; 0.4; 50; 50. 9; 0.4; 50; 50. 9.1; 0.4; 10; 90. 15; 0.4; 10; 90.
Flow Rate:	0.4 mL/min
Solvent A:	100% water; 0.1% formic acid
Solvent B:	100% acetonitrile; 0.1% formic acid
Chromatography Type:	HILIC

MS:

MS ID:	MS007001
Analysis ID:	AN007307
Instrument Name:	Waters Synapt-XS
Instrument Type:	QTOF
MS Type:	ESI
MS Comments:	Normalized in Progenesis
Ion Mode:	POSITIVE