Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity
Abstract
:1. Introduction
2. Experimental Design, Materials and Methods
2.1. Study Participants
2.2. Measurements of Glucose Regulation
2.3. Oral Glucose Tolerance Test
2.4. Measurement of Muscle, Liver, and Adipose Tissue Insulin Resistance
2.5. Body Fat Composition, Abdominal Fat Distribution and Liver Fat
2.6. Biochemical Measurements in Blood
2.7. Targeted Metabolomics
2.8. Untargeted Lipidomics
2.9. Lipid Identification
2.10. Data Processing and Analysis
3. Results
3.1. Cohort Characteristics
3.2. Associations between Clinical Variables, Fat Deposition, and Insulin Resistance Phenotypes
3.3. Plasma Omics Signature of Clinical and Metabolic Traits
3.4. Metabolomics Correlates of Clinical Phenotypes of Obesity
4. Discussion
4.1. Biomarkers Aligning with Muscle Insulin Resistance
4.2. Biomarkers Aligning with Liver Insulin Resistance
4.3. Biomarkers Aligning with Adipose Tissue Insulin Resistance
4.4. Biomarkers Aligning with Abdominal Fat Depots
4.5. Study Limitations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Class of Measurement | Characteristic | Mean/Median (± SD or IQR) | Min-Max Values |
---|---|---|---|
N (M/F) | 62 (27/35) | ||
Age (years) | 50.5 ± 11.4 | 21–69 | |
Body mass, fat composition and distribution | BMI (kg.m−2) | 36.3 ± 4.5 | 30.9–48.5 |
Waist circumference (cm) | 111 ± 14 | 85–155 | |
Body fat (% of total mass) | 48 (40, 52) | 31–61 | |
Visceral fat (cm3) | 249 (212, 320) | 139–492 | |
Subcutaneous fat (cm2) | 501 (418, 596) | 265–835 | |
Liver fat (%) | 10.6 (5.9, 21.3) | 0.7–63.5 | |
Blood pressure | Systolic (mm Hg) | 125 ± 13 | 100–169 |
Diastolic (mm Hg) | 82 ± 9 | 59–106 | |
Serum lipids | Total cholesterol (mmol.L−1) | 4.9 ± 0.8 | 3.1–7.1 |
LDL cholesterol (mmol.L−1) | 3.0 ± 0.7 | 1.5–5.0 | |
HDL cholesterol (mmol.L−1) | 1.3 ± 0.3 | 0.8–2.0 | |
Triglycerides (mmol.L−1) | 1.1 ± 0.4 | 0.4–2.5 | |
NEFA (mmol.L−1) | 0.4 ± 0.1 | 0.1–0.7 | |
Glucose regulation | HbA1c (mmol/mol) | 36 ± 3 | 29–43 |
HbA1c (%) | 5.5 ± 0.3 | 4.8–6.1 | |
Fasting blood glucose (mmol.L−1) | 4.8 ± 0.4 | 3.5–6.0 | |
2-hour blood glucose (mmol.L−1) | 6.3 ± 1.6 | 2.7–10.1 | |
Individuals with IFG (n) | 1 | ||
Individuals with IGT (n) | 12 | ||
Individuals with IFG and IGT (n) | 2 | ||
Individuals with HbA1c ≥ 5.7% | 21 | ||
Fasting insulin (mU.L−1) | 16.5 (11.3, 27.4) | 5.9–73.4 | |
HOMA-IR | 3.4 (2.2, 6.2) | 1.2–19.6 | |
EGP (mg.kg−1.min−1) | 2.1 ± 0.3 | 1.4–2.8 | |
EGP suppression (%) | 65 ± 14 | 30–93 | |
GIR/FFM (M-value, µmol.min−1.kg−1) | 90 ± 30 | 24–186 | |
NEFA suppression (%) | 32 ± 13 | 10–62 | |
Serum insulin during the clamp (mU.L−1) | Low dose clamp | 42 ± 13 | 19–86 |
High dose clamp | 212 ± 44 | 131–296 | |
Medication use | Individuals treated with anti-hypertensive medications (n (%)) | 13 (21) | |
Individuals treated with lipid reducing agents (n (%)) | 8 (13) |
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Koay, Y.C.; Coster, A.C.F.; Chen, D.L.; Milner, B.; Batarseh, A.; O’Sullivan, J.F.; Greenfield, J.R.; Samocha-Bonet, D. Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity. Metabolites 2022, 12, 1272. https://doi.org/10.3390/metabo12121272
Koay YC, Coster ACF, Chen DL, Milner B, Batarseh A, O’Sullivan JF, Greenfield JR, Samocha-Bonet D. Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity. Metabolites. 2022; 12(12):1272. https://doi.org/10.3390/metabo12121272
Chicago/Turabian StyleKoay, Yen Chin, Adelle C. F. Coster, Daniel L. Chen, Brad Milner, Amani Batarseh, John F. O’Sullivan, Jerry R. Greenfield, and Dorit Samocha-Bonet. 2022. "Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity" Metabolites 12, no. 12: 1272. https://doi.org/10.3390/metabo12121272
APA StyleKoay, Y. C., Coster, A. C. F., Chen, D. L., Milner, B., Batarseh, A., O’Sullivan, J. F., Greenfield, J. R., & Samocha-Bonet, D. (2022). Metabolomics and Lipidomics Signatures of Insulin Resistance and Abdominal Fat Depots in People Living with Obesity. Metabolites, 12(12), 1272. https://doi.org/10.3390/metabo12121272