Tumor Necrosis Receptor Superfamily Interact with Fusion and Fission of Mitochondria of Adipose Tissue in Obese Patients without Type 2 Diabetes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Serum/Plasma Blood Studying
2.2. Gene Expression Research
2.3. Western Blot Analysis
2.4. Statistical Analysis
3. Results
3.1. Biochemical Parameters of Obese Patients
3.2. The Concentration of Plasma Cytokines of the TNF Receptor Superfamily in Obese Patients
3.3. The NF-kB Levels in Obese Patients
3.4. Mitochondrial Dynamics—Division and Fusion
3.5. TNF Receptors and Ligands Levels Have Been Associated with Components of Mitochondrial Dynamics
3.6. TNF-a Level Was Associated with MFN2 Gene Expression in GO
4. Discussion
5. Conclusions
- Increased levels of receptors sTNF-R1, sTNF-R2, TNFRSF8, and ligands TNFSF12, TNFSF13, TNFSF13B are signs of obese patients without T2DM.
- The TNFSF12 and TNFSF13B levels were associated with NFkB1 gene expression in GO in obese patients, and NFkB1 gene expression increased in GO and SAT in obese patients without T2DM compared with the control group. The NFkB1 gene expression was associated with components of mitochondrial dynamic—DNM1L, MFN2, and TFAM gene expression in GO and SAT in all obese patients.
- The DNM1L, MFN2, and TFAM gene expression levels in GO and SAT responsible for regulating mitochondrial dynamics were increased in obese patients without T2DM, and DNM1L and TFAM proteins production were unbalanced in patients with obesity and T2DM.
- The TNFSF12 levels contributed to an increase in MFN2 gene expression in GO; TNFSF13 contributed to an increase in DNM1L gene expression in GO; TNFSF13B contributed to an increase in TFAM gene expression in GO.
- The TNF-a levels in blood plasma were associated with a decrease in MFN2 gene expression in GO and IL-10 in blood plasma.
- The TNFSF12 levels contributed to a decrease in glucose levels, a decrease in BMI, and an increase in IL-10 levels by influencing the MFN2 gene expression in GO, which supports mitochondrial fusion.
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene Name | Sequences of Primers and Probes |
---|---|
RPLPO | F: 5′-GGCGACCTGGAAGTCCAACT-3′ R: 5′-CCATCAGCACCACAGCCTTC-3′ Bgl635-5′-ATCTGCTGCATCTGCTTGGAGCCCA-3′-BHQ-2 |
NFkB1 | F: 5′-CAGGAAGATGTGGTGGAGGA-3′ R: 5′-TGGGGTGGTCAAGAAGTAGTG-3′ FAM-5′-CCTTCTGGACCGCTTGGGTAACTCTGT-3′-BHQ-1 |
TFAM | F: 5′-CGCTCCCCCTTCAGTTTTGT-3′ R: 5′-TACCTGCCACTCCGCCCTAT-3′ FAM-5′-CGAGGTGGTTTTCATCTGTCTTGGCA-3′-BHQ-1 |
DNM1L | F: 5′-TCTGGAGGTGGTGGGGTTG-3′ R: 5′-TGGGTTTTGATTTTTCTTCTGCTAAT-3′ FAM-5′-ACCAACCACAGGCAACTGGAGAGGA-3′-BHQ-1 |
MFN2 | F: 5′-CCAGCGTCCCATCCCTCT-3′ R: 5′-TCCACACCACTCCTCCAACA-3′ FAM-5′-ACAGGGCTCGCTCACCCAGGAG-3′-BHQ-1 |
Cytokine (pg/mL) | Control Group (n = 16) | Obese Patients without T2DM (n = 41) | Obese Patients with T2DM (n = 45) |
---|---|---|---|
TNF-a | 2.120 (1.56–3.120) | 14.71 (10.44–16.89) p1–2 < 0.001 * | 32.86 (20.15–34.42) p1–3 < 0.001 * p2–3 < 0.001 * |
sTNF-R1 | 110.36 (89.41–229.08) | 591.57 (187.88–1229.37) p1–2 < 0.001 * | 96.1 (53.05–134.83) p1–3 = 0.021 * p2–3 < 0.001 * |
sTNF-R2 | 59.39 (48.03–111.73) | 206.92 (107.19–288.66) p1–2 < 0.001 * | 86.10 (52.21–137.23) p2–3 < 0.001 * |
sTNFRSF8 | 31.82 (22.61–50.17) | 65.13 (34.26–116.48) p1–2 < 0.001 * | 23.01 (14.51–35.53) p1–3 = 0.023 * p2–3 < 0.001 * |
TNFSF12 | 347.33 (247.81–464.02) | 541.25 (278.36–691.23) p1–2 = 0.050* | 64.15 (39.54–103.46) p1–3 < 0.001 * p2–3 < 0.001 * |
TNFSF13 | 20,872.63 (17,224.93–31,761.95) | 48,896.8 (28,910.78–80,400.51) p1–2 < 0.001 * | 14,131.77 (8361.43–20,974.42) p1–3 = 0.001 * p2–3 < 0.001 * |
TNFSF13B | 2103.81 (1565.48–3381.11) | 3411.06 (2610.11–5571.37) p1–2 < 0.001 * | 1387.88 (921.86–2135.25) p1–3 = 0.001 * p2–3 < 0.001* |
IL-10 | 0.64 (0.32–1.53) | 2.18 (1.11–3.44) p1–2 = 0.001 * | 0.75 (0.26–0.99) p2–3 < 0.001 * |
Multiple Regression | Dependent Variable | Independent Variable | β | Standard Error | t-Value | p-Value |
---|---|---|---|---|---|---|
Multiple regression linear Model 1 Multiple R-squared = 0.167, Adjusted R-squared = 0.141, p-value = 0.0026 | sTNF-R1 | BMI | −0.297 | 0.105 | −2.819 | 0.0063 * |
Glucose | −0.241 | 0.110 | −2.179 | 0.0329 * | ||
Multiple regression linear Model 2 Multiple R-squared = 0.466, Adjusted R-squared = 0.438, p-value < 0.0001 | TNFSF12 | BMI | −0.325 | 0.082 | −3.927 | 0.0002 * |
Glucose | −0.262 | 0.085 | −3.082 | 0.0031 * | ||
IL10 | 0.439 | 0.122 | 3.585 | 0.0006 * | ||
Multiple regression linear Model 3 Multiple R-squared = 0.290, Adjusted R-squared = 0.252, p-value = 0.0001 * | TNFSF13B | BMI | −0.251 | 0.093 | −2.693 | 0.0092 * |
Glucose | −0.196 | 0.095 | −2.052 | 0.0447 * | ||
IL10 | 0.341 | 0.137 | 2.479 | 0.0161 * |
Multiple Regression | Dependent Variable | Independent Variable | β | Standard Error | t-Value | p-Value |
---|---|---|---|---|---|---|
Multiple regression linear Model 4 Multiple R-squared = 0.626 Adjusted R-squared = 0.574 p-value < 0.0001 * | TNFSF12 | BMI | −0.217 | 0.087 | −2.493 | 0.0186 * |
Glucose | −0.208 | 0.094 | −2.204 | 0.0356 * | ||
IL10 | 0.334 | 0.149 | 2.246 | 0.0324 * | ||
MFN2 in GO | 0.359 | 0.103 | 3.478 | 0.0016 * |
Multiple Regression | Dependent Variable | Independent Variable | β | Standard Error | t-Value | p-Value |
---|---|---|---|---|---|---|
Multiple regression linear Model 5 Multiple R-squared = 0.702, Adjusted R-squared = 0.665, p-value = 6.123 × 10−5 | TNF-a | IL10 | −0.576 | 0.239 | −2.404 | 0.0286 * |
MFN2 in GO | −0.526 | 0.112 | −4.695 | 0.0001 * |
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Shunkina, D.; Komar, A.; Vulf, M.; Quang, H.V.; Shunkin, E.; Kirienkova, E.; Dakchnevich, A.; Malkov, D.; Zatolokin, P.; Litvinova, L. Tumor Necrosis Receptor Superfamily Interact with Fusion and Fission of Mitochondria of Adipose Tissue in Obese Patients without Type 2 Diabetes. Biomedicines 2021, 9, 1260. https://doi.org/10.3390/biomedicines9091260
Shunkina D, Komar A, Vulf M, Quang HV, Shunkin E, Kirienkova E, Dakchnevich A, Malkov D, Zatolokin P, Litvinova L. Tumor Necrosis Receptor Superfamily Interact with Fusion and Fission of Mitochondria of Adipose Tissue in Obese Patients without Type 2 Diabetes. Biomedicines. 2021; 9(9):1260. https://doi.org/10.3390/biomedicines9091260
Chicago/Turabian StyleShunkina (Skuratovskaia), Daria, Alexandra Komar, Maria Vulf, Hung Vu Quang, Egor Shunkin, Elena Kirienkova, Anastasiia Dakchnevich, Danil Malkov, Pavel Zatolokin, and Larisa Litvinova. 2021. "Tumor Necrosis Receptor Superfamily Interact with Fusion and Fission of Mitochondria of Adipose Tissue in Obese Patients without Type 2 Diabetes" Biomedicines 9, no. 9: 1260. https://doi.org/10.3390/biomedicines9091260