Summary of study ST001607

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 PR001032. The data can be accessed directly via it's Project DOI: 10.21228/M89D63 This work is supported by NIH grant, U2C- DK119886.

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Study IDST001607
Study TitleGenetic background shapes phenotypic response to diet for adiposity in the Collaborative Cross
Study TypeDiet challenge
Study SummaryDefined as chronic excessive accumulation of adiposity, obesity results from long-term imbalance between energy intake and expenditure. The mechanisms behind how caloric imbalance occurs are complex and influenced by numerous biological and environmental factors, especially genetics and diet. Population-based diet recommendations have had limited success partly due to the wide variation in physiological responses across individuals when they consume the same diet. Thus, it is necessary to broaden our understanding of how individual genetics and diet interact relative to the development of obesity for improving weight loss treatment. To determine how consumption of diets with different macronutrient composition alter adiposity and other obesity-related traits in a genetically diverse population, we analyzed body composition, metabolic rate, clinical blood chemistries, and circulating metabolites in 22 strains of mice from the Collaborative Cross (CC), a highly diverse recombinant inbred mouse population, before and after 8 weeks of feeding either a high protein or high fat high sucrose diet. At both baseline and post-diet, adiposity and other obesity-related traits exhibited a broad range of phenotypic variation based on CC strain; diet-induced changes in adiposity and other traits also depended largely on CC strain. In addition to estimating heritability at baseline, we also quantified the effect size of diet for each trait, which varied by trait and experimental diet. Our findings identified CC strains prone to developing obesity, demonstrate the genotypic and phenotypic diversity of the CC for studying complex traits, and highlight the importance of accounting for genetic differences when making dietary recommendations.
Institute
USDA
DepartmentObesity and metabolism research unit
LaboratoryBennett's Lab
Last NameBennett
First NameBrian
Address430 West Health Sciences Dr. Davis, Ca, 95616
Emailbrian.bennett@usda.gov
Phone(530) 754-4417
Submit Date2020-11-05
Total Subjects202
Num Females202
Raw Data AvailableYes
Raw Data File Type(s).wiff
Analysis Type DetailLC-MS
Release Date2020-12-31
Release Version1
Brian Bennett Brian Bennett
https://dx.doi.org/10.21228/M89D63
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP001690
Sampleprep Summary:Baseline and post-diet circulating trimethylamine N-oxide (TMAO), choline, phosphocholine, betaine, and carnitine were quantified using liquid chromatography–mass spectrometry (LC-MS) methods described by Wang et al. (2014) with modifications (Wang et al., 2014. Analytical Biochemistry 455 (June 2014): 35–40. https://doi.org/10.1016/j.ab.2014.03.016.). Briefly, samples (20 µl plasma) were aliquoted to a 2 ml Eppendorf tube and mixed with 80 µl of 5 µM surrogate standard comprised of deuterated analytes in methanol. Standards ranging from 0 µM to 100 µM of non-deuterated analytes in methanol were run in order to establish analyte standard curves. Two-fold serial dilutions of a 100 µM stock solution in methanol was used to make 13 standards. To prepare standards for sample quantification, 80 µl of 5 µM SSTD and 20 µl of each standard were aliquoted directly to the glass inserts in HPLC vials and briefly vortexed. Prior to acquisition, samples and standards were vortexed for 30 seconds and centrifuged at 18,000 g at 10°C for 10 min. Supernatant (5 µl) was transferred to 150 µl glass inserts in High Performance Liquid Chromatography (HPLC) vials and analyzed by injection onto a silica column (150 by 2 mm, 3 um particle Silica (2) with 100 Angstrom; Catalog #00F-41620-B0, Phenomenex, Torrance, CA) at a flow rate of 0.25 ml/min using a Waters Acquity UPLC (Waters, Milford, MA) interfaced with an API 4000 Q-TRAP mass spectrometer (AB SCIEX, Framingham, MA). A discontinuous gradient was generated to resolve the analytes by mixing solvent A (0.1% acetic acid in water) with solvent B (0.1% acetic acid in methanol) at different ratios starting from 2% B linearly to 15% B over 5 min, then linearly to 100% B to 6.25 min, then hold to 8 min, and then back to 2% B at 6.25 min and held until 10 min.
Sampleprep Protocol Filename:phoebeyam_SP_protocol.pdf
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