An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins
Abstract
:1. Introduction
2. Results
2.1. Sample Preparation and Peptide Selection
2.2. Assay Development
2.2.1. Quantification Characteristics and Reproducibility of the MRM Method
2.2.2. Application of the MRM Assay: Analysis of Human Serum from Adults
2.2.3. Validation of the MRM Method
2.3. Further Application of the MRM Method
2.3.1. Analysis of Human Serum Samples from Children
2.3.2. Analysis of Cell Culture Supernatants from Mature Human Adipocytes
3. Discussion
4. Material and Methods
4.1. Ethic Statement
4.2. Reagents Chemicals and Serum Samples
4.3. Human Serum from Adults and Children
4.3.1. Protein Depletion
4.3.2. Proteolytic Cleavage of Human Serum
4.4. Human Preadipocytes (SGBS Cells)
4.4.1. Differentiation of Human Preadipocytes
4.4.2. Proteolytic Cleavage of Cell Culture Supernatant
4.5. NanoRP-UPLC-MS/MS
4.6. Selection of Potential Candidate Peptides
4.7. Data Analysis
4.8. Validation of MRM-Based Method Using ELISA
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: The mass spectrometry data have been deposited to the PRIDE Archive via PRIDE partner repository (PXD013829). |
Protein | External Calibration Curve | LOD | LLOQ | ||||
---|---|---|---|---|---|---|---|
Slope | Intercept | R2 | Peptide (ng/mL) | Protein (ng/mL) | Peptide (ng/mL) | Protein (ng/mL) | |
Adipsin | 3.11104 | 1.41106 | 0.97 | 0.63 | 21.63 | 1.88 | 64.88 |
Adiponectin | 3.22104 | −7.72104 | 0.99 | 0.71 | 13.21 | 2.13 | 39.62 |
Asprosin | 2.11104 | −4.50106 | 0.96 | 6.02 | 85.00 | 18.05 | 255.00 |
Chemerin | 9.71104 | −5.97105 | 0.99 | 1.91 | 27.93 | 5.74 | 83.78 |
Leptin | 9.71104 | −5.97105 | 0.99 | 2.30 | 37.28 | 6.89 | 111.85 |
PAI-1 | 3.78105 | −1.29106 | 0.99 | 0.34 | 22.53 | 1.03 | 67.59 |
Progranulin | 7.53104 | 2.08105 | 0.99 | 0.50 | 31.77 | 1.51 | 95.32 |
RBP-4 | 1.27105 | −2.54106 | 0.99 | 30.09 | 575.25 | 90.27 | 1725.75 |
Vaspin | 1.20105 | −9.41104 | 0.99 | 0.44 | 23.59 | 1.31 | 70.76 |
Apo-A1 | 7.32103 | −6.99105 | 0.98 | 46.86 | 1025.93 | 140.57 | 3077.80 |
Apo-A2 | 5.08104 | 3.12105 | 0.99 | 1.58 | 18.63 | 4.74 | 55.88 |
Apo-A4 | 1.97104 | 3.55104 | 0.99 | 1.65 | 75.67 | 4.94 | 227.00 |
Apo-B100 | 1.62104 | 8.44103 | 0.99 | 1.91 | 859.34 | 5.72 | 2578.03 |
Apo-C1 | 2.69103 | −4.43104 | 0.99 | 4.04 | 31.11 | 12.11 | 93.32 |
Apo-C2 | 6.02104 | 5.98105 | 0.99 | 1.73 | 18.81 | 5.20 | 56.42 |
Apo-C3 | 5.00103 | −1.19105 | 0.99 | 20.03 | 180.87 | 60.08 | 542.60 |
Apo-C4 | 3.65104 | −7.26104 | 0.99 | 1.80 | 24.26 | 5.39 | 72.77 |
Apo-D | 4.03104 | 2.40105 | 0.99 | 2.06 | 35.46 | 6.18 | 106.38 |
Apo-E | 1.30104 | −1.47105 | 0.99 | 5.01 | 120.51 | 15.03 | 361.54 |
Protein | MRM | Literature (ELISA) |
---|---|---|
Adipsin | 15.2–711.4 ng/mL | 467–5148 ng/mL [57,58] |
Adiponectin | 0.1–1.1 µg/mL | 0.02–10.3 µg/mL [70,71,80] |
Chemerin | 120.3–139.4 ng/mL | 0.6–204.8 ng/mL [24,69,81] |
Leptin | 112.2–134.84 ng/mL | 1.2–101.3 ng/mL [71,72,81,82] |
PAI-1 | 46.01–78.5 ng/mL | 1.8–270 ng/mL [65,66,67,68] |
Progranulin | 84.1–178.9 ng/mL | 5.2–386.0 ng/mL [59,74,83] |
RBP-4 | 3.5–23.8 µg/mL | 1.5–163 µg/mL [22,55,56,84] |
Vaspin | 32.6–181.7 ng/mL | 0.3–17.9 ng/mL [61,62,63,64,82] |
Normal Weight (n = 25) | Obese (n = 25) | |
---|---|---|
Sex (w/m) | 21/4 | 16/9 |
Age (years) | 51.2 ± 18.0 | 54.1 ± 11.2 |
Body weight (kg) | 61.3 ± 10.2 | 129.0 ± 21.7 |
BMI (kg/m2) | 21.7 ± 2.5 | 46.6 ± 6.4 |
HDL-cholesterol (mmol/L) | 1.7 ± 0.4 | 1.3 ± 0.3 |
LDL-cholesterol (mmol/L) | 3.2 ± 0.8 | 3.6 ± 0.8 |
Type 2 Diabetes (yes/no) | 6/19 | 19/6 |
Girls (n = 64) | Boys (n = 44) | |
---|---|---|
Age (years) | 12.8 ± 3.6 | 12.2 ± 3.2 |
BMI (SDS) | −0.3 ± 0.8 | −0.2 ± 0.7 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Krieg, L.; Schaffert, A.; Kern, M.; Landgraf, K.; Wabitsch, M.; Beck-Sickinger, A.G.; Körner, A.; Blüher, M.; von Bergen, M.; Schubert, K. An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins. Molecules 2020, 25, 775. https://doi.org/10.3390/molecules25040775
Krieg L, Schaffert A, Kern M, Landgraf K, Wabitsch M, Beck-Sickinger AG, Körner A, Blüher M, von Bergen M, Schubert K. An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins. Molecules. 2020; 25(4):775. https://doi.org/10.3390/molecules25040775
Chicago/Turabian StyleKrieg, Laura, Alexandra Schaffert, Matthias Kern, Kathrin Landgraf, Martin Wabitsch, Annette G. Beck-Sickinger, Antje Körner, Matthias Blüher, Martin von Bergen, and Kristin Schubert. 2020. "An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins" Molecules 25, no. 4: 775. https://doi.org/10.3390/molecules25040775