Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Study Design
2.3. Laboratory Measurements
2.4. Multi-Analyte Profiling of Metabolic Cytokines
2.5. Sample Size Analysis
2.6. Statistical Analysis
3. Results
3.1. Effect of Group and Obesity on Clinical and Biochemical Variables in the Fasting State
3.2. Effect of Oral Macronutrient Challenges on Metabolic Cytokine Concentrations
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Finanzierung
Conflicts of Interest
References
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Control Women | Women with PCOS (Polycystic Ovary Syndrome) | Control Men | Group | Obesity | Interaction | ||||
---|---|---|---|---|---|---|---|---|---|
Non-obese (n = 9) | Obese (n = 8) | Non-obese (n = 9) | Obese (n = 8) | Non-obese (n = 10) | Obese (n = 9) | P | P | P | |
Age (years) | 26 ± 5 | 27 ± 6 | 24 ± 8 | 30 ± 4 | 24 ± 5 | 25 ± 4 | 0.342 | 0.101 | 0.319 |
Body mass index (kg/m2) | 23 ± 2 | 36 ± 4 | 24 ± 2 | 37 ± 5 | 23 ± 2 | 34 ± 3 | 0.226 | <0.001 | 0.782 |
Waist circumference (cm) | 76 ± 9 | 100 ± 17 | 72 ± 7 | 105 ± 11 | 81 ± 5 | 110 ± 13 | 0.049 B,C | <0.001 | 0.377 |
Waist to hip ratio | 0.75 ± 0.08 | 0.83 ± 0.12 | 0.73 ± 0.05 | 0.85 ± 0.06 | 0.83 ± 0.04 | 0.90 ± 0.05 | 0.002 B, C | <0.001 | 0.436 |
Hirsutism score | 1.4 ± 1.3 | 1.8 ± 1.2 | 9.7 ± 4.5 | 9.3 ± 4.5 | - | - | <0.001 A | 0.738 | 0.876 |
Total testosterone (ng/dL) | 46 ± 9 | 58 ± 14 | 72 ± 20 | 69 ± 29 | 534 ± 96 | 499 ± 104 | <0.001 A,B,C | 0.776 | 0.196 |
Free testosterone (ng/dL) | 0.6 ± 0.2 | 0.9 ± 0.0 | 1.0 ± 0.4 | 1.3 ± 0.7 | 13.0 ± 3.0 | 13.4 ± 2.7 | <0.001 A,B,C | 0.024 | 0.265 |
Total estradiol (pg/mL) | 41 ± 17 | 75 ± 55 | 50 ± 55 | 41 ± 13 | 19 ± 4 | 26 ± 7 | <0.001 B,C | 0.024 | 0.422 |
Free estradiol (pg/mL) | 0.74 ± 0.30 | 1.44 ± 0.82 | 0.98 ± 1.17 | 0.93 ± 0.38 | 0.49 ± 0.14 | 0.71 ± 0.19 | 0.010 B | 0.003 | 0.520 |
Ratio FT/FE2 | 8.6 ± 0.9 | 7.6 ± 1.6 | 17.4 ± 4.0 | 14.0 ± 1.9 | 263.4 ± 22.6 | 186.4 ± 12.7 | <0.001 A,B,C | 0.119 | 0.750 |
SHBG (µg/dL) | 504 ± 225 | 387 ± 126 | 450 ± 189 | 288 ± 117 | 243 ± 90 | 180 ± 54 | <0.001 B,C | 0.008 | 0.568 |
Androstendione (ng/mL) | 2.6 ± 0.8 | 2.7 ± 0.8 | 4.2 ± 1.2 | 3.8 ± 1.8 | 2.0 ± 0.5 | 2.7 ± 1.1 | <0.001 A,C | 0.712 | 0.371 |
DHEAS (ng/mL) | 1990 ± 442 | 1953 ± 553 | 2800 ± 1437 | 2100 ± 774 | 2211 ± 663 | 3021 ± 1068 | 0.094 | 0.852 | 0.081 |
hsCRP (mg/L) | 2.8 ± 2.3 | 4.0 ± 2.9 | 2.1 ± 2.2 | 6.8 ± 7.7 | 3.3 ± 2.6 | 3.2 ± 1.3 | 0.998 | 0.009 | 0.207 |
Fasting insulin (µIU/mL) | 7.9 ± 2.9 | 11.1 ± 3.0 | 7.5 ± 4.2 | 13.5 ± 3.6 | 5.8 ± 1.6 | 10.8 ± 3.9 | 0.123 | <0.001 | 0.440 |
Fasting glucose (mg/dL) | 85 ± 7 | 96 ± 7 | 81 ± 9 | 87 ± 9 | 88 ± 9 | 94 ± 7 | 0.011 A,C | 0.001 | 0.408 |
HOMA-IR | 1.6 ± 0.6 | 2.6 ± 0.7 | 1.5 ± 0.9 | 2.9 ± 0.7 | 1.3 ± 0.4 | 2.5 ± 1.0 | 0.424 | <0.001 | 0.742 |
Insulin sensitivity index | 6.6 ± 2.9 | 3.3 ± 1.2 | 8.1 ± 4.7 | 3.5 ± 1.4 | 7.3 ± 2.8 | 3.8 ± 1.6 | 0.640 | <0.001 | 0.909 |
Triglycerides (mg/dL) | 75 ± 32 | 81 ± 30 | 80 ± 22 | 101 ± 42 | 79 ± 26 | 102 ± 35 | 0.399 | 0.054 | 0.711 |
Total cholesterol (mg/dL) | 170 ± 35 | 181 ± 35 | 166± 39 | 170 ± 35 | 158 ± 23 | 185 ± 35 | 0.844 | 0.133 | 0.485 |
HDL-cholesterol (mg/dL) | 54 ± 12 | 51 ± 8 | 54 ± 8 | 46 ± 8 | 46 ± 8 | 39 ± 4 | 0.001 B, C | 0.002 | 0.512 |
LDL-cholesterol (mg/dL) | 104 ± 31 | 112 ± 23 | 97 ± 31 | 104 ± 31 | 93 ± 15 | 127 ± 31 | 0.507 | 0.034 | 0.237 |
Control Women | Women with PCOS | Control Men | Group | Obesity | Interaction | |||||
---|---|---|---|---|---|---|---|---|---|---|
Non-obese (n = 9) | Obese (n = 8) | Non-obese (n = 9) | Obese (n = 8) | Non-obese (n = 9) | Obese (n = 9) | P | P | P | ||
Omentin-1 (ng/mL) | 215 ± 48 | 201 ± 75 | 211 ± 45 | 196 ± 86 | 259 ± 47 | 201 ± 89 | 0.573 | 0.044 | 0.561 | |
Vaspin (pg/mL) | 324 ± 159 | 249 ± 185 | 349 ± 482 | 278 ± 180 | 169 ± 123 | 133 ± 61 | 0.022 A,B | 0.472 | 0.672 | |
Lipocalin-2 (ng/mL) | 108 ± 23 | 187 ± 72 | 180 ± 95 | 150 ± 65 | 122 ± 54 | 121 ± 29 | 0.152 | 0.203 | 0.049 | |
Adipsin (µg/mL) | 2.87 ± 0.51 | 3.46 ± 0.50 | 3.42 ± 0.89 | 3.58 ± 0.56 | 3.20 ± 0.46 | 3.47 ± 0.84 | 0.359 | 0.054 | 0.533 | |
PAI-1 (ng/mL) | 28.2 ± 15.9 | 60.0 ± 13.8 | 33.2 ± 15.0 | 48.8 ± 22.8 | 21.2 ± 14.6 | 44.4 ± 26.6 | 0.093 | < 0.001 | 0.424 | |
Chemerin (ng/mL) | 8.14 ± 1.54 | 10.48 ± 2.02 | 8.49 ± 1.91 | 9.32 ± 1.30 | 8.13 ± 1.73 | 8.53 ± 1.60 | 0.240 | 0.015 | 0.224 | |
FGF-21 (pg/mL) | 392 ± 169 | 338 ± 144 | 285 ± 78 | 349 ± 84 | 258 ± 128 | 308 ± 179 | 0.102 | 0.489 | 0.346 | |
FGF-23 (pg/mL) | 312 ± 172 | 187 ± 41 | 237 ± 134 | 195 ± 45 | 222 ± 111 | 171 ± 19 | 0.282 | 0.013 | 0.394 |
Macronutrient | Omentin-1 | Vaspin | Lipocalin-2 | Adipsin | PAI-1 | Chemerin | FGF-21 | FGF-23 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
r | p | r | p | r | p | r | p | r | p | r | p | r | p | r | p | |
All subjects as a whole | ||||||||||||||||
Glucose | −0.359 | 0.009 | −0.573 | <0.001 | −0.319 | 0.021 | −0.612 | <0.001 | −0.567 | <0.001 | −0.379 | 0.006 | −0.272 | 0.051 | −0.395 | 0.004 |
Lipids | −0.456 | 0.001 | -0.505 | <0.001 | −0.249 | 0.076 | −0.661 | <0.001 | −0.426 | 0.002 | −0.430 | 0.001 | - | - | −0.567 | <0.001 |
Proteins | - | - | -0.594 | <0.001 | −0.460 | 0.001 | −0.512 | <0.001 | −0.594 | <0.001 | −0.284 | 0.041 | −0.437 | 0.001 | −0.349 | 0.011 |
Non-obese subjects | ||||||||||||||||
Glucose | - | - | −0.615 | 0.001 | - | - | −0.751 | <0.001 | −0.490 | 0.009 | - | - | - | - | −0.346 | 0.077 |
Lipids | −0.589 | 0.001 | −0.688 | <0.001 | - | - | −0.636 | <0.001 | - | - | −0.514 | 0.006 | - | - | −0.638 | <0.001 |
Proteins | −0.473 | 0.013 | −0.734 | <0.001 | −0.330 | 0.092 | −0.419 | 0.030 | - | - | - | - | −0.400 | 0.039 | −0.563 | 0.002 |
Obese subjects | ||||||||||||||||
Glucose | −0.456 | 0.022 | −0.590 | 0.002 | −0.455 | 0.022 | −0.418 | 0.037 | −0.657 | <0.001 | −0.528 | 0.007 | −0.536 | 0.006 | −0.702 | <0.001 |
Lipids | - | - | - | - | −0.604 | 0.001 | −0.651 | <0.001 | −0.502 | 0.011 | −0.370 | 0.069 | - | - | −0.398 | 0.049 |
Proteins | 0.494 | 0.012 | −0.579 | 0.002 | −0.598 | 0.002 | −0.633 | 0.001 | −0.733 | <0.001 | −0.369 | 0.069 | −0.476 | 0.016 | - | - |
Serum Concentrations | Fasting | Postprandial (AUC) |
---|---|---|
Omentin-1 | ↓ in obese | ↓ after all macronutrient loads (mainly in non-obese after proteins) |
Vaspin | ↓ in men | ↓ during lipid challenge and ↓↓ during protein load Global effect of obesity (smaller response in obese) |
Lipocalin-2 | ↑ in obese only in control women PCOS > control women only in non-obese | ↓ during glucose and protein loads |
Adipsin | Trends towards ↑ in obese | ↓ after all macronutrient loads |
PAI-1 | ↑↑ in obese | ↓ during lipid challenge and ↓↓ during protein load Global effect of obesity (larger response in obese) |
Chemerin | ↑ in obese | ↓ during glucose and lipid challenges |
FGF-21 | - | ↑ during glucose, ↓ during lipid challenge and ↓↓ during protein loads |
FGF-23 | ↓ in obese | ↓ during protein load, only in non-obese individuals |
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Martínez-García, M.Á.; Moncayo, S.; Insenser, M.; Álvarez-Blasco, F.; Luque-Ramírez, M.; Escobar-Morreale, H.F. Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex. Nutrients 2019, 11, 2566. https://doi.org/10.3390/nu11112566
Martínez-García MÁ, Moncayo S, Insenser M, Álvarez-Blasco F, Luque-Ramírez M, Escobar-Morreale HF. Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex. Nutrients. 2019; 11(11):2566. https://doi.org/10.3390/nu11112566
Chicago/Turabian StyleMartínez-García, M. Ángeles, Samuel Moncayo, María Insenser, Francisco Álvarez-Blasco, Manuel Luque-Ramírez, and Héctor F. Escobar-Morreale. 2019. "Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex" Nutrients 11, no. 11: 2566. https://doi.org/10.3390/nu11112566