Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro
Abstract
:1. Introduction
- the detailed CTRP-3 mRNA expression profile in subcutaneous and visceral adipose tissue samples obtained from severely obese patients undergoing bariatric surgery,
- basal CTRP-3 serum concentrations in obese patients and their changes after bariatric surgery or during LCD,
- correlations of adipose tissue CTRP-3 gene expression with its circulating protein concentrations and with a broad panel of anthropometric and biochemical parameters by univariate and multivariate analysis,
- effects of bile acids and incretins on CTRP-3 expression in adipocytes in vitro.
2. Results
2.1. Study Populations
2.2. Baseline CTRP-3 Serum Concentrations and CTRP-3 Gene Expression in Adipose Tissue of Obese Subjects
2.3. Correlation Analysis of Baseline Data
2.4. Significant Decline of CTRP-3 Serum Concentrations After Intervention
2.5. Correlation Analysis of Adipose Tissue CTRP-3 and Bile Acid Receptor Gene Expression
2.6. Bile Acid Sub-Species Exert Differential Effects on CTRP-3 mRNA Expression in Adipocytes In Vitro
2.7. GLP-1 Treatment Downregulates CTRP-3 Gene Expression in Adipocytes
2.8. Adipocyte CTRP-3 mRNA Expression is Unresponsive to Simvastatin
2.9. CTRP-3 and Bile Acid Receptor Gene Expression in the Murine System
3. Discussion
4. Materials and Methods
4.1. The ROBS Study Cohort (Research in Obesity and Bariatric Surgery)
4.2. Serum Measurement of CTRP-3 Concentrations
4.3. Cell Culture Experiments
4.4. Adipose Tissue and Adipocyte mRNA Extraction
4.5. Real-Time PCR Analysis of CTRP-3 and Bile Acid Receptor mRNA Expression
- Human CTRP-3: 5′-GCCCCAGTATCAGGTGTGTA-3′/5′-GCAAAGGTGGAGAAGCGTTG-3′;
- Murine CTRP-3: 5′-GGGGTTCTTTATGGAGCATT-3′/5′-AAATGCATCCTTTGAGGTGA-3′;
- Human TGR5: 5′-CACTGTTGTCCCTCCTCTCC-3′/5′-ACACTGCTTTGGCTGCTTG-3′;
- Murine TGR5: 5′-GAGCGTCGCCCACCACTAGG-3′/5′-CGCTGATCACCCAGCCCCATG-3′;
- Murine FXR I (for adipocyte mRNA): 5′-TGGGCTCCGAATCCTCTTAGA-3′/5′-TGGTCCTCAAATAAGATCCTTGG-3′;
- Murine FXR II (for adipose tissue mRNA): 5′-GTACAAGTGTAAGAACGGGG-3′/5′-CTTGGTTGTGGAGGTCACTT-3′.
4.6. Animals
4.6.1. Tissues from Wildtype and CTRP-3 Knockout Mice
4.6.2. Isolation and Cell Culture of Primary Murine Adipocytes
4.6.3. Intraperitoneal Application of Recombinant CTRP-3 in Mice
4.6.4. Data Base and Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Cohort | Mean BMI (kg/m2) | Mean CTRP-3 Serum Concentrations (ng/ml) | ELISA Supplier | Study | Reference |
---|---|---|---|---|---|
Bariatric surgery (n = 179) | 53.3 ± 6.9 | 106.5 ± 51.0 | CTRP-3 DuoSet ELISA, R&D system, Wiesbaden, Germany | Schmid, A. et al. | present |
Low calorie diet (n = 131) | 43.5 ± 6.7 | 108.1 ± 40.5 | CTRP-3 DuoSet ELISA, R&D system, Wiesbaden, Germany | Schmid, A. et al. | present |
Obesity subgroup (n = 180) | 28.02 ± 1.65 | 94.53 ± 43.94 | CTRP-3 ELISA Aviscera Bioscience, Santa Clara, CA, USA | Deng, W. et al. | [14] |
Obesity subgroup (n = 44) | 45.2 ± 1.1 | 405 ± 8.3 | CTRP-3 ELISA AdipoGen, Incheon, Korea | Wolf, R.M. et al. | [13] |
Obesity subgroup (n = 30) | 33.7 ± 4.4 | 258.22 ± 147.62 | CTRP-3 ELISA Wuhan El Aab Science Co. | Jain, N.B. et al. | [24] |
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A—Correlation Analysis of | rho | p |
Serum CTRP-3 concentrations in BS patients with | ||
CTRP-3 gene expression in sc AT | +0.23 | 0.003 |
CTRP-3 gene expression in vis AT | +0.16 | 0.033 |
Adiponectin (µg/ml) | +0.38 | <0.001 |
Leptin (ng/ml) | +0.16 | 0.033 |
B—Correlation Analysis of | rho | p |
Serum CTRP-3 concentrations in LCD patients with | ||
Adiponectin (µg/mL) | +0.32 | <0.001 |
Leptin (ng/mL) | +0.23 | 0.007 |
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Schmid, A.; Gehl, J.; Thomalla, M.; Hochberg, A.; Kreiß, A.; Patz, M.; Karrasch, T.; Schäffler, A. Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro. Int. J. Mol. Sci. 2020, 21, 8168. https://doi.org/10.3390/ijms21218168
Schmid A, Gehl J, Thomalla M, Hochberg A, Kreiß A, Patz M, Karrasch T, Schäffler A. Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro. International Journal of Molecular Sciences. 2020; 21(21):8168. https://doi.org/10.3390/ijms21218168
Chicago/Turabian StyleSchmid, Andreas, Jonas Gehl, Miriam Thomalla, Alexandra Hochberg, Anja Kreiß, Marissa Patz, Thomas Karrasch, and Andreas Schäffler. 2020. "Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro" International Journal of Molecular Sciences 21, no. 21: 8168. https://doi.org/10.3390/ijms21218168
APA StyleSchmid, A., Gehl, J., Thomalla, M., Hochberg, A., Kreiß, A., Patz, M., Karrasch, T., & Schäffler, A. (2020). Downregulation of CTRP-3 by Weight Loss In Vivo and by Bile Acids and Incretins in Adipocytes In Vitro. International Journal of Molecular Sciences, 21(21), 8168. https://doi.org/10.3390/ijms21218168