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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001607 |
| Study Title | Genetic background shapes phenotypic response to diet for adiposity in the Collaborative Cross |
| Study Type | Diet challenge |
| Study Summary | Defined 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 |
| Department | Obesity and metabolism research unit |
| Laboratory | Bennett's Lab |
| Last Name | Bennett |
| First Name | Brian |
| Address | 430 West Health Sciences Dr. Davis, Ca, 95616 |
| brian.bennett@usda.gov | |
| Phone | (530) 754-4417 |
| Submit Date | 2020-11-05 |
| Total Subjects | 202 |
| Num Females | 202 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-12-31 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001032 |
| Project DOI: | doi: 10.21228/M89D63 |
| Project Title: | Genetic background shapes phenotypic response to diet for adiposity in the Collaborative Cross |
| Project Summary: | Defined 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 |
| Department: | Obesity and metabolism research unit |
| Laboratory: | Bennett's Lab |
| Last Name: | Bennett |
| First Name: | Brian |
| Address: | 430 West Health Sciences Drive, DAVIS, CA, 95616, USA |
| Email: | brian.bennett@usda.gov |
| Phone: | (530) 754-4417 |
Subject:
| Subject ID: | SU001684 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | 22 strains from the Collaborative Cross (CC) mouse panel |
| Gender: | Female |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Diet |
|---|---|---|
| SA136047 | P 238 | AIN-76A | TimePoint:baseline |
| SA136048 | P 237 | AIN-76A | TimePoint:baseline |
| SA136049 | P 240 | AIN-76A | TimePoint:baseline |
| SA136050 | P 242 | AIN-76A | TimePoint:baseline |
| SA136051 | P 243 | AIN-76A | TimePoint:baseline |
| SA136052 | P 236 | AIN-76A | TimePoint:baseline |
| SA136053 | P 234 | AIN-76A | TimePoint:baseline |
| SA136054 | P 228 | AIN-76A | TimePoint:baseline |
| SA136055 | P 230 | AIN-76A | TimePoint:baseline |
| SA136056 | P 231 | AIN-76A | TimePoint:baseline |
| SA136057 | P 233 | AIN-76A | TimePoint:baseline |
| SA136058 | P 245 | AIN-76A | TimePoint:baseline |
| SA136059 | P 249 | AIN-76A | TimePoint:baseline |
| SA136060 | P 261 | AIN-76A | TimePoint:baseline |
| SA136061 | P 260 | AIN-76A | TimePoint:baseline |
| SA136062 | P 263 | AIN-76A | TimePoint:baseline |
| SA136063 | P 264 | AIN-76A | TimePoint:baseline |
| SA136064 | P 266 | AIN-76A | TimePoint:baseline |
| SA136065 | P 258 | AIN-76A | TimePoint:baseline |
| SA136066 | P 257 | AIN-76A | TimePoint:baseline |
| SA136067 | P 227 | AIN-76A | TimePoint:baseline |
| SA136068 | P 251 | AIN-76A | TimePoint:baseline |
| SA136069 | P 252 | AIN-76A | TimePoint:baseline |
| SA136070 | P 254 | AIN-76A | TimePoint:baseline |
| SA136071 | P 246 | AIN-76A | TimePoint:baseline |
| SA136072 | P 224 | AIN-76A | TimePoint:baseline |
| SA136073 | P 197 | AIN-76A | TimePoint:baseline |
| SA136074 | P 195 | AIN-76A | TimePoint:baseline |
| SA136075 | P 198 | AIN-76A | TimePoint:baseline |
| SA136076 | P 200 | AIN-76A | TimePoint:baseline |
| SA136077 | P 201 | AIN-76A | TimePoint:baseline |
| SA136078 | P 191 | AIN-76A | TimePoint:baseline |
| SA136079 | P 189 | AIN-76A | TimePoint:baseline |
| SA136080 | P 183 | AIN-76A | TimePoint:baseline |
| SA136081 | P 185 | AIN-76A | TimePoint:baseline |
| SA136082 | P 186 | AIN-76A | TimePoint:baseline |
| SA136083 | P 188 | AIN-76A | TimePoint:baseline |
| SA136084 | P 203 | AIN-76A | TimePoint:baseline |
| SA136085 | P 204 | AIN-76A | TimePoint:baseline |
| SA136086 | P 216 | AIN-76A | TimePoint:baseline |
| SA136087 | P 218 | AIN-76A | TimePoint:baseline |
| SA136088 | P 219 | AIN-76A | TimePoint:baseline |
| SA136089 | P 221 | AIN-76A | TimePoint:baseline |
| SA136090 | P 215 | AIN-76A | TimePoint:baseline |
| SA136091 | P 213 | AIN-76A | TimePoint:baseline |
| SA136092 | P 207 | AIN-76A | TimePoint:baseline |
| SA136093 | P 209 | AIN-76A | TimePoint:baseline |
| SA136094 | P 210 | AIN-76A | TimePoint:baseline |
| SA136095 | P 212 | AIN-76A | TimePoint:baseline |
| SA136096 | P 267 | AIN-76A | TimePoint:baseline |
| SA136097 | P 269 | AIN-76A | TimePoint:baseline |
| SA136098 | P 119 | AIN-76A | TimePoint:baseline |
| SA136099 | P 116 | AIN-76A | TimePoint:baseline |
| SA136100 | P 120 | AIN-76A | TimePoint:baseline |
| SA136101 | P 126 | AIN-76A | TimePoint:baseline |
| SA136102 | P 137 | AIN-76A | TimePoint:baseline |
| SA136103 | P 114 | AIN-76A | TimePoint:baseline |
| SA136104 | P 104 | AIN-76A | TimePoint:baseline |
| SA136105 | P 92 | AIN-76A | TimePoint:baseline |
| SA136106 | P 93 | AIN-76A | TimePoint:baseline |
| SA136107 | P 96 | AIN-76A | TimePoint:baseline |
| SA136108 | P 98 | AIN-76A | TimePoint:baseline |
| SA136109 | P 164 | AIN-76A | TimePoint:baseline |
| SA136110 | P 176 | AIN-76A | TimePoint:baseline |
| SA136111 | P 255 | AIN-76A | TimePoint:baseline |
| SA136112 | P 275 | AIN-76A | TimePoint:baseline |
| SA136113 | P 2 | AIN-76A | TimePoint:baseline |
| SA136114 | P 320 | AIN-76A | TimePoint:baseline |
| SA136115 | P 248 | AIN-76A | TimePoint:baseline |
| SA136116 | P 225 | AIN-76A | TimePoint:baseline |
| SA136117 | P 192 | AIN-76A | TimePoint:baseline |
| SA136118 | P 194 | AIN-76A | TimePoint:baseline |
| SA136119 | P 206 | AIN-76A | TimePoint:baseline |
| SA136120 | P 222 | AIN-76A | TimePoint:baseline |
| SA136121 | P 87 | AIN-76A | TimePoint:baseline |
| SA136122 | P 86 | AIN-76A | TimePoint:baseline |
| SA136123 | P 284 | AIN-76A | TimePoint:baseline |
| SA136124 | P 282 | AIN-76A | TimePoint:baseline |
| SA136125 | P 285 | AIN-76A | TimePoint:baseline |
| SA136126 | P 302 | AIN-76A | TimePoint:baseline |
| SA136127 | P 303 | AIN-76A | TimePoint:baseline |
| SA136128 | P 281 | AIN-76A | TimePoint:baseline |
| SA136129 | P 279 | AIN-76A | TimePoint:baseline |
| SA136130 | P 270 | AIN-76A | TimePoint:baseline |
| SA136131 | P 272 | AIN-76A | TimePoint:baseline |
| SA136132 | P 273 | AIN-76A | TimePoint:baseline |
| SA136133 | P 278 | AIN-76A | TimePoint:baseline |
| SA136134 | P 305 | AIN-76A | TimePoint:baseline |
| SA136135 | P 306 | AIN-76A | TimePoint:baseline |
| SA136136 | P 344 | AIN-76A | TimePoint:baseline |
| SA136137 | P 352 | AIN-76A | TimePoint:baseline |
| SA136138 | P 353 | AIN-76A | TimePoint:baseline |
| SA136139 | P 74 | AIN-76A | TimePoint:baseline |
| SA136140 | P 343 | AIN-76A | TimePoint:baseline |
| SA136141 | P 338 | AIN-76A | TimePoint:baseline |
| SA136142 | P 321 | AIN-76A | TimePoint:baseline |
| SA136143 | P 334 | AIN-76A | TimePoint:baseline |
| SA136144 | P 335 | AIN-76A | TimePoint:baseline |
| SA136145 | P 337 | AIN-76A | TimePoint:baseline |
| SA136146 | P 182 | AIN-76A | TimePoint:baseline |
Collection:
| Collection ID: | CO001677 |
| Collection Summary: | Blood was drawn from the mice after a 2-week acclimation period (baseline) and after 8 weeks (postdiet) on either a high protein (H-Protein) or high fat high sucrose (H-Sucrose). Blood samples were collected via retro-orbital bleed with heparinized capillary tubes into EDTA tubes, placed on ice, and centrifuged at 6000 rpm for 10 minutes at 4°C for plasma collection. Plasma was then transferred to 1.5 ml Eppendorf tubes and stored at -80°C. |
| Sample Type: | Blood (plasma) |
| Collection Method: | retro-orbital bleed with heparinized capillary tubes |
| Storage Conditions: | Described in summary |
| Collection Vials: | EDTA tubes |
Treatment:
| Treatment ID: | TR001697 |
| Treatment Summary: | Approximately 4-5 mice were assigned to either the high protein (H-Protein) or high fat high sucrose (H-Sucrose) diet per strain for 8 weeks. |
| Treatment: | Diet challenge |
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 |
Combined analysis:
| Analysis ID | AN002640 |
|---|---|
| Analysis type | MS |
| Chromatography type | Normal phase |
| Chromatography system | Waters Acquity UPLC |
| Column | Luna Silica (150 x 2mm,3m) |
| MS Type | ESI |
| MS instrument type | QTRAP |
| MS instrument name | ABI Sciex API 4000 QTrap |
| Ion Mode | POSITIVE |
| Units | micromolar |
Chromatography:
| Chromatography ID: | CH001950 |
| Chromatography Comments: | Phenomenex Luna 3 µm Silica (2) 100 Å, LC Column 150 x 2 mm |
| Instrument Name: | Waters Acquity UPLC |
| Column Name: | Luna Silica (150 x 2mm,3m) |
| Column Temperature: | Room Temperature |
| Flow Rate: | 0.25 ml/min |
| Sample Injection: | 5 µL |
| Solvent A: | 100% water; 0.1% acetic acid |
| Solvent B: | 100% methanol; 0.1% acetic acid |
| Weak Wash Solvent Name: | 70% water, 20% methanol, 10% 2-propanol |
| Strong Wash Solvent Name: | 50:50 Acetonitrile:Methanol |
| Chromatography Type: | Normal phase |
MS:
| MS ID: | MS002452 |
| Analysis ID: | AN002640 |
| Instrument Name: | ABI Sciex API 4000 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | Analytes were monitored using electrospray ionization in positive-ion mode with multiple reaction monitoring (MRM) of precursor and characteristic production transitions as shown in MS_protocol.pdf. The parameters for the ion monitoring were as follows: spray voltage, 4.5 kV; curtain gas, 15; GS1, 60; GS2, 50; CAD gas, medium; Nitrogen (99.95% purity) was used as the source and collision gas. Integration and quantification of values was done using Analyst 1.6.2 software (AB SCIEX, Singapore). Standard linearity was calculated using linear regression model. Please see LC_protocol.pdf and MS_protocol.pdf for additional details. |
| Ion Mode: | POSITIVE |
| Analysis Protocol File: | phoebeyam_LC_protocol.pdf |
