Deep Multi-OMICs and Multi-Tissue Characterization in a Pre- and Postprandial State in Human Volunteers: The GEMM Family Study Research Design
Abstract
:1. Introduction
2. Materials and Methods
2.1. Recruitment of Study Participants
2.2. Study Timeline and Standardization of Postprandial Procedures
2.2.1. First Visit
2.2.2. Second Visit (14 Days after the First Visit)
2.3. Anthropometric Measurement, Body Composition and Indirect Calorimetry
2.4. Mixed Meal Challenge
2.5. Hormone, Cytokine and Clinical Chemistry Measurements for Postprandial Metabolic Assessments
2.6. Fasting and Postprandial Plasma Metabolomic Profiling of Amino Acids and Acylcarnitines
2.7. Acylcarnitines
2.8. Transcriptomics: RNA Gene Expression Profiling
2.9. Statistical Analysis
2.10. Interpretation and Power
2.11. Correction for Admixture
3. Results
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Lower BMI Values (n = 8) | Higher BMI Values (n = 8) | |
---|---|---|
24 ± 1.6 | 32.1 ± 5.7 | |
Anthropometric and Clinical Measurements | ||
Age | 34.1 ± 14.4 | 41.2 ± 11.0 |
Height (cm) | 152.4 ± 6.0 | 151.9 ± 3.6 |
Weight (kg) | 56.1 ± 7.9 | 74.1 ± 14.0 |
Waist Circumference (cm) | 76.6 ± 4.5 | 95.3 ± 11.4 |
Fat Total (%) | 39.1 ± 4.5 | 46.5 ± 4.7 |
Fat Mass Total (kg) | 20.9 ± 5.0 | 33.4 ± 8.3 |
Muscle Mass Total (kg) | 31.9 ± 3.2 | 37.8 ± 6.3 |
Avg. Systolic Pressure (mmHg) | 107.7 ± 7.8 | 109.6 ± 12.5 |
Avg. Diastolic Pressure (mmHg) | 67.5 ± 3.9 | 70.8 ± 7.7 |
Adipose Tissue Hormones | ||
Fasting Adiponectin (µg/mL) | 19.9 ± 13.2 | 22.6 ± 19.6 |
Fasting Leptin (ng/mL) | 8.6 ± 5.6 | 18.6 ± 9.3 |
Postprandial Leptin (30 min) | 7.9 ± 5.1 | 18.0 ± 9.9 |
Postprandial Leptin (60 min) | 8.1 ± 5.0 | 17.8 ± 9.4 |
Postprandial Leptin (120 min) | 8.5 ± 5.9 | 16.6 ± 9.1 |
Postprandial Leptin (180 min) | 9.3 ± 6.1 | 16.7 ± 8.1 |
Postprandial Leptin (300 min) | 9.4 ± 5.9 | 16.4 ± 8.2 |
Gastrointestinal Satiety Signals | ||
Fasting GLP1 | 121.9 ± 56.8 | 136.3 ± 45.5 |
Postprandial GLP1 30 min | 147.9 ± 48.8 | 189.5 ± 63.1 |
Postprandial GLP1 60 min | 123.0 ±47.6 | 151.1 ± 58.2 |
Postprandial GLP1 120 min | 130.4 ± 53.1 | 143.8 ± 64.2 |
Postprandial GLP1 180 min | 120.4 ± 49.1 | 138.8 ± 51.6 |
Postprandial GLP1 300 min | 123.1 ± 61.8 | 145.0 ± 64.6 |
Fasting PYY | 54.2 ± 46.5 | 35.1± 51.2 |
Postprandial PYY 30 min | 70.6 ± 24.8 | 121.2 ± 74.8 |
Postprandial PYY 60 min | 83.8 ± 65.3 | 94.3 ± 52.8 |
Postprandial PYY 120 min | 75.7 ± 52.1 | 79.7 ± 51.8 |
Postprandial PYY 180 min | 82.1 ± 56.3 | 86.8 ± 63.7 |
Postprandial PYY 300 min | 75.8 ± 44.8 | 76.1 ± 66.5 |
Fasting Ghrelin | 333.5 ± 59.1 | 233.1 ± 137.2 |
Postprandial Ghrelin 30 min | 274.1 ± 50.2 | 192.2 ± 127.2 |
Postprandial Ghrelin 60 min | 220.9 ± 41.2 | 166.1 ± 116.6 |
Postprandial Ghrelin 120 min | 206.7 ± 44.6 | 155.6 ± 106.1 |
Postprandial Ghrelin 180 min | 211 ± 66.4 | 152.9 ± 108.9 |
Postprandial Ghrelin 300 min | 249.6 ± 76.4 | 157.2 ± 124.8 |
Adipocytokines and Inflammatory Biomarkers | ||
TNFα | 1.4 ± 1.1 | 1.8 ± 0.7 |
hs-CPR | 0.09 ± 0.07 | 0.42 ± 0.30 |
PAI-1 | 43,527.9 ± 38,563.4 | 66,901.4 ± 56,005.3 |
IL-6 | 1.9 ± 1.3 | 2.1 ± 1.6 |
Lower BMI Values (n = 8) | Higher BMI Values (n = 8) | |
---|---|---|
24 ± 1.6 | 32.1 ± 5.7 | |
Insulin-Glucose Axis | ||
Fasting Glucose (mg/dL) | 84.3 ± 4.9 | 87.9 ± 7.0 |
Postprandial Glucose (30 min) (mg/dL) | 116.5 ± 9.57 | 107.8 ± 11.4 |
Postprandial Glucose (60 min) (mg/dL) | 119.25 ± 27.09 | 115.62 ± 13.83 |
Postprandial Glucose (120 min) (mg/dL) | 114.5 ± 17.07 | 115.62 ± 19.15 |
Postprandial Glucose (180 min) (mg/dL) | 101.25 ± 16.42 | 99.37 ± 9.83 |
Postprandial Glucose (300 min) (mg/dL) | 93.62 ± 14.16 | 92.25 ± 4.65 |
Fasting Insulin (uIU/mL) | 11.04 ± 10.01 | 16.64 ± 10.41 |
Postprandial Insulin (30 min) (uIU/mL) | 63.81 ± 29.78 | 78.29 ± 42.78 |
Postprandial Insulin (60 min) (uIU/mL) | 72.53 ± 42.82 | 84.03 ± 60.51 |
Postprandial Insulin (120 min) (uIU/mL) | 51.09 ± 22.65 | 54.27 ± 36.19 |
Postprandial Insulin (180 min) (uIU/mL) | 31.46 ± 12.45 | 41.85 ± 25.79 |
Postprandial Insulin (300 min) (uIU/mL) | 16.94 ± 14.40 | 27.65 ± 18.52 |
HOMA-IR | 2.31 ± 2.17 | 3.68 ± 2.34 |
Matsuda Index | 6.66 ± 4.05 | 4.89 ± 3.59 |
Lipid-Lipoprotein Metabolism | ||
Fasting NEFA (mEq/L) | 0.7 ± 0.1 | 0.7 ± 0.1 |
Postprandial NEFA (30 min) (mEq/L) | 0.5 ± 0.2 | 0.7 ± 0.1 |
Postprandial NEFA (60 min) (mEq/L) | 0.2 ± 0.1 | 0.4 ± 0.2 |
Postprandial NEFA (120 min) (mEq/L) | 0.1 ± 0.1 | 0.2 ± 0.1 |
Postprandial NEFA (180 min) (mEq/L) | 0.1 ± 0.1 | 0.3 ± 0.2 |
Postprandial NEFA (300 min) (mEq/L) | 0.5 ± 0.3 | 0.5 ± 0.2 |
Fasting Triglyceride (mg/dL) | 89.9 ± 27.2 | 161.7 ± 47.0 |
Postprandial Triglyceride (30 min) (mg/dL) | 84.3 ± 27.0 | 157.6 ± 33.6 |
Postprandial Triglyceride (60 min) (mg/dL) | 90.6 ± 27.3 | 165.1 ± 41.1 |
Postprandial Triglyceride (120 min) (mg/dL) | 92.4 ± 31.2 | 186.8 ± 55.4 |
Postprandial Triglyceride (180 min) (mg/dL) | 103.0 ± 39.1 | 209.1 ± 75.3 |
Postprandial Triglyceride (300 min) (mg/dL) | 108.1 ± 44.0 | 204.8 ± 61.2 |
Fasting HDL-Col | 58.5 ± 13.6 | 48.9 ± 6.4 |
Postprandial HDL-Col (180 min) | 55.0 ± 14.3 | 46.8 ± 6.3 |
Postprandial HDL-Col (300 min) | 55.6 ± 15.1 | 46.3 ± 6.6 |
Lower BMI Values (n = 8) | Higher BMI Values (n = 8) | |
---|---|---|
24 ± 1.6 | 32.1 ± 5.7 | |
Metabolomics Profiling | ||
Targeted Aminoacid Signature | ||
Branched-chain (BCCA) amino acids | ||
Isoleucine 0 min | 42.5 ± 7.2 | 41.8 ± 5.0 |
Isoleucine 30 min | 73.3 ± 14.5 | 51.6 ± 11.28 |
Isoleucine 180 min | 63.1 ± 10.8 | 50.1 ± 8.5 |
Isoleucine 300 min | 55.5 ± 6.6 | 50.6 ± 9.7 |
Leucine 0 min | 77.8 ± 10.2 | 80.8 ± 14.7 |
Leucine 30 min | 125.3 ± 19.8 | 95.6 ± 21.1 |
Leucine 180 min | 99.8 ± 13.6 | 85.8 ± 15.6 |
Leucine 300 min | 88.1 ± 9.7 | 81.02 ± 12.9 |
Valine 0 min | 141.9 ± 24.7 | 153.1 ± 38.9 |
Valine 30 min | 183.9 ± 34.9 | 167.1 ± 47.8 |
Valine 180 min | 171.4 ± 22.2 | 159.4 ± 36.6 |
Valine 300 min | 162.4 ± 11.2 | 159.5 ± 32.3 |
Phenylalanine 0 min | 43.05 ± 3.13 | 53. 7 ± 8.1 |
Phenylalanine 30 min | 57.3 ± 5.7 | 59.6 ± 8.8 |
Phenylalanine 180 min | 53.9 ± 4.9 | 56.9 ± 7.8 |
Phenylalanine 300 min | 48.2 ± 5.01 | 55.3 ± 7.5 |
Aspartic acid 0 min | 3.9 ± 2.1 | 6.1 ± 1.6 |
Aspartic acid 30 min | 2.7 ± 1.7 | 3.7 ± 2.2 |
Aspartic acid 180 min | 2.3 ± 1.5 | 2.5 ± 2 |
Aspartic acid 300 min | 3.05 ± 1.2 | 4.6 ± 2.5 |
Targeted Acylcarnitine Signature | ||
Acylcarnitine (14:0) 0 min | 0.2 ± 0.07 | 0.2 ± 0.06 |
Acylcarnitine (14:0) 30 min | 0.2 ± 0.6 | 0.2 ± 0.06 |
Acylcarnitine (14:0) 180 min | 0.07 ± 0.02 | 0.1 ± 0.07 |
Acylcarnitine (14:0) 300 min | 0.09 ± 0.06 | 0.1 ± 0.05 |
Acylcarnitine (14:1) 0 min | 0.7 ± 0.5 | 0.1 ± 0.2 |
Acylcarnitine (14:1) 30 min | 0.7 ± 0.5 | 0.1 ± 0.1 |
Acylcarnitine (14:1) 180 min | 0.2 ± 0.2 | 0.04 ± 0.04 |
Acylcarnitine (14:1) 300 min | 0.4 ± 0.4 | 0.03 ± 0.02 |
Acylcarnitine (14:2) 0 min | 0.6 ± 0.3 | 0.2 ± 0.05 |
Acylcarnitine (14:2) 30 min | 0.4 ± 0.2 | 0.2 ± 0.06 |
Acylcarnitine (14:2) 180 min | 0.2 ± 0.08 | 0.2 ± 0.09 |
Acylcarnitine (14:2) 300 min | 0.3 ± 0.3 | 0.2 ± 0.02 |
Acylcarnitine (14:3) 0 min | 0.06 ± 0.03 | 0.03 ± 0.005 |
Acylcarnitine (14:3) 30 min | 0.05 ± 0.02 | 0.02 ± 0.003 |
Acylcarnitine (14:3) 180 min | 0.03 ± 0.01 | 0.02 ± 0.01 |
Acylcarnitine (14:3) 300 min | 0.05 ± 0.04 | 0.02 ± 0.005 |
Acylcarnitine (16:0) 0 min | 1.6 ± 0.2 | 1.5 ± 0.3 |
Acylcarnitine (16:0) 30 min | 1.4 ± 0.2 | 1.5 ± 0.3 |
Acylcarnitine (16:0) 180 min | 0.8 ± 0.2 | 1.2 ± 0.4 |
Acylcarnitine (16:0) 300 min | 0.8 ± 0.1 | 1.1 ± 0.3 |
Probe | Accession | Gene Symbol | p-Value | Direction of Change |
---|---|---|---|---|
ILMN_1684982 | NM_002612.3 | PDK4 | 0.00000106 | up |
ILMN_1697448 | NM_006472.2 | TXNIP | 0.0000279 | up |
ILMN_1791728 | NM_052901.2 | SLC25A25 | 0.000232157 | down |
ILMN_1663092 | NM_006079.3 | CITED2 | 0.000454775 | up |
ILMN_1691846 | NM_015714.2 | G0S2 | 0.000530702 | down |
ILMN_1661519 | NM_014702.3 | KIAA0408 | 0.000559434 | up |
ILMN_1907042 | AK123264 | C1orf132 | 0.000903385 | up |
ILMN_1794017 | NM_013376.3 | SERTAD1 | 0.00102915 | down |
ILMN_1728699 | NM_194285.2 | SPTY2D1 | 0.001347097 | down |
ILMN_1874689 | AB074162 | MIR181A2HG | 0.001811776 | down |
ILMN_1797031 | NM_024610.4 | HSPBAP1 | 0.002114313 | up |
ILMN_1860963 | BM715829 | transcribed locus | 0.00277532 | down |
ILMN_1710284 | NM_005524.2 | HES1 | 0.002894267 | down |
ILMN_1839665 | BQ186372 | transcribed locus | 0.002993048 | up |
ILMN_1908530 | AW003529 | miR-205 | 0.003042844 | down |
ILMN_1776483 | GDS5231 | no annotation | 0.003499501 | up |
ILMN_1689212 | NM_001010892.1 | RSHL3 | 0.004134486 | down |
ILMN_2186061 | NM_004566.2 | PFKFB3 | 0.004236655 | up |
ILMN_1870041 | AJ227862 | partial mRNA | 0.004322057 | up |
ILMN_1771618 | NM_173671.1 | FLJ37396 | 0.004436233 | down |
ILMN_3266471 | GDS5431 | no annotation | 0.005104923 | down |
ILMN_2077680 | NM_152353.1 | CLDND2 | 0.005149724 | up |
ILMN_1764873 | NM_001419.2 | ELAVL1 | 0.005480716 | down |
ILMN_1756006 | NM_015104.1 | ATG2A | 0.005654292 | up |
ILMN_3262439 | GDS5167 | no annotation | 0.006327375 | down |
ILMN_1732750 | NM_016565.2 | CHCHD8 | 0.006543098 | down |
ILMN_1704022 | NM_207316.1 | TMEM207 | 0.006752015 | down |
ILMN_2044927 | NM_006913.2 | RNF5 | 0.007227478 | down |
ILMN_1741392 | NM_000387.3 | SLC25A20 | 0.007466004 | up |
ILMN_1786242 | GDS3855 | no annotation | 0.008237115 | up |
ILMN_1836309 | GDS3531 | no annotation | 0.008873484 | down |
ILMN_3245678 | NC_000001.11 | RNU1-1 | 0.009334803 | up |
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Bastarrachea, R.A.; Laviada-Molina, H.A.; Nava-Gonzalez, E.J.; Leal-Berumen, I.; Escudero-Lourdes, C.; Escalante-Araiza, F.; Peschard, V.-G.; Veloz-Garza, R.A.; Haack, K.; Martínez-Hernández, A.; et al. Deep Multi-OMICs and Multi-Tissue Characterization in a Pre- and Postprandial State in Human Volunteers: The GEMM Family Study Research Design. Genes 2018, 9, 532. https://doi.org/10.3390/genes9110532
Bastarrachea RA, Laviada-Molina HA, Nava-Gonzalez EJ, Leal-Berumen I, Escudero-Lourdes C, Escalante-Araiza F, Peschard V-G, Veloz-Garza RA, Haack K, Martínez-Hernández A, et al. Deep Multi-OMICs and Multi-Tissue Characterization in a Pre- and Postprandial State in Human Volunteers: The GEMM Family Study Research Design. Genes. 2018; 9(11):532. https://doi.org/10.3390/genes9110532
Chicago/Turabian StyleBastarrachea, Raul A., Hugo A. Laviada-Molina, Edna J. Nava-Gonzalez, Irene Leal-Berumen, Claudia Escudero-Lourdes, Fabiola Escalante-Araiza, Vanessa-Giselle Peschard, Rosa A. Veloz-Garza, Karin Haack, Angélica Martínez-Hernández, and et al. 2018. "Deep Multi-OMICs and Multi-Tissue Characterization in a Pre- and Postprandial State in Human Volunteers: The GEMM Family Study Research Design" Genes 9, no. 11: 532. https://doi.org/10.3390/genes9110532