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Role of ChREBP and SREBP-1c in gestational diabetes: two key players in glucose and lipid metabolism

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International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Background

Gestational diabetes mellitus (GDM) is any degree of glucose intolerance diagnosed during pregnancy. Metabolic abnormalities in GDM are associated with pancreatic β-cell destruction and decreased insulin sensitivity. Carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c) are two transcription factors that play a key role in carbohydrate and lipid metabolism homeostasis. Our aim in this study was to elucidate the role of these proteins in GDM.

Methods

The study included 50 pregnant women diagnosed with GDM and 52 pregnant women with normal glucose tolerance. Maternal blood samples were collected from pregnant women between the 24th and 28th weeks of pregnancy. Serum SREBP-1c and ChREBP levels were measured with commercial ELISA kits according to the manufacturer’s instructions.

Results

Serum ChREBP (p=0.044) and SREBP1c (p=0.042) levels of pregnant women with normal glucose tolerance were found to be statistically significantly higher than women with GDM.

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References

  1. Mirghani Dirar A, Doupis J. Gestational diabetes from A to Z. World J Diabetes. 2017;8(12):489–511. https://doi.org/10.4239/wjd.v8.i12.489.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Alfadhli EM. Gestational diabetes mellitus. Saudi Med J. 2015;36(4):399–406. https://doi.org/10.15537/smj.2015.4.10307.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sheikh A, Sheikh L. Changing prealence of gestational diabetes mellitus during pregnancy over more than a decade. J Pak Med Assoc. 2020;70(8):1477–8. https://doi.org/10.5455/jpma.65585.

    Article  PubMed  Google Scholar 

  4. McIntyre HD, Catalano P, Zhang C, Desoye G, Mathiesen ER, Damm P. Gestational diabetes mellitus. Nat Rev Dis Primers. 2019;5(1):47. https://doi.org/10.1038/s41572-019-0098-8.

    Article  PubMed  Google Scholar 

  5. Chelakkadan M. P N. A review article-gestational diabetes mellitus. J Curr Pharm Res. 2016;9:1. https://doi.org/10.22159/ijcpr.2017v9i1.16615.

    Article  CAS  Google Scholar 

  6. Linden AG, Li S, Choi HY, Fang F, Fukasawa M, Uyeda K, Hammer RE, Horton JD, Engelking LJ, Liang G. Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. J Lipid Res. 2018;59(3):475–87. https://doi.org/10.1194/jlr.M081836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ortega-Prieto P, Postic C. Carbohydrate sensing through the transcription factor ChREBP. Frontiers in Genetics Review. 2019;10(472). https://doi.org/10.3389/fgene.2019.00472.

  8. Dorotea D, Koya D, Ha H. Recent insights into SREBP as a direct mediator of kidney fibrosis via lipid-independent pathways. Frontiers in Pharmacology Review. 2020;11(265). https://doi.org/10.3389/fphar.2020.00265.

  9. Wang Y, Viscarra J, Kim S-J, Sul HS. Transcriptional regulation of hepatic lipogenesis. Nature Reviews Molecular Cell Biology. 2015;16(11):678–89. https://doi.org/10.1038/nrm4074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shimomura I, Hammer RE, Richardson JA, Ikemoto S, Bashmakov Y, Goldstein JL, Brown MS. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. 1998;12(20):3182–94. https://doi.org/10.1101/gad.12.20.3182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lizuka K, Miller B, Uyeda K. Deficiency of carbohydrate-activated transcription factor ChREBP prevents obesity and improves plasma glucose control in leptin-deficient (ob/ob) mice. Am J Physiol Endocrinol Metab. 2006;291(2):E358–64. https://doi.org/10.1152/ajpendo.00027.2006.

    Article  CAS  Google Scholar 

  12. López-Oliva M, Martínez E. SREBP-1c, ChREBP and LXR: their role in the pathogenesis of the non-alcoholic fatty liver. An R Acad Nac Farm. 2014;80:14–48. https://doi.org/10.14218/JCTH.2017.00061.

    Article  Google Scholar 

  13. Wen YA, Xiong X, Zaytseva YY, Napier DL, Vallee E, Li AT, Wang C, Weiss HL, Evers BM, Gao T. Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer. Cell Death Dis. 2018;9(3):265. https://doi.org/10.1038/s41419-018-0330-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Song Z, Yang H, Zhou L, Yang F. Glucose-sensing transcription factor MondoA/ChREBP as targets for type 2 diabetes: opportunities and challenges. Int J Mol Sci. 2019;20(20). https://doi.org/10.3390/ijms20205132.

  15. Hurtado del Pozo C, Vesperinas-García G, Rubio M, Corripio-Sánchez R, Torres-García AJ, Obregon MJ, et al. ChREBP expression in the liver, adipose tissue and differentiated preadipocytes in human obesity. Biochim Biophys Acta. 2011;1811(12):1194–200. https://doi.org/10.1016/j.bbalip.2011.07.016.

    Article  CAS  PubMed  Google Scholar 

  16. Chen Y, Wang Y-J, Zhao Y, Wang J-C. Carbohydrate response element binding protein (ChREBP) modulates the inflammatory response of mesangial cells in response to glucose. Bioscience Reports. 2018;38(6). https://doi.org/10.1042/bsr20180767.

  17. Dentin R, Benhamed F, Hainault I, Fauveau V, Foufelle F, Dyck JR, et al. Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice. Diabetes. 2006;55(8):2159–70. https://doi.org/10.2337/db06-0200.

    Article  CAS  PubMed  Google Scholar 

  18. Benhamed F, Denechaud P-D, Lemoine M, Robichon C, Moldes M, Bertrand-Michel J, et al. The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans. J Clin Invest. 2012;122(6):2176–94. https://doi.org/10.1172/JCI41636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fisher FM, Kim M, Doridot L, Cunniff JC, Parker TS, Levine DM, et al. A critical role for ChREBP-mediated FGF21 secretion in hepatic fructose metabolism. Mol Metab. 2017;6(1):14–21. https://doi.org/10.1016/j.molmet.2016.11.008.

    Article  CAS  PubMed  Google Scholar 

  20. Herman MA, Peroni OD, Villoria J, Schön MR, Abumrad NA, Blüher M, et al. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature. 2012;484(7394):333–8. https://doi.org/10.1038/nature10986.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vijayakumar A, Aryal P, Wen J, Syed I, Vazirani RP, Moraes-Vieira PM, et al. Absence of carbohydrate response element binding protein in adipocytes causes systemic insulin resistance and impairs glucose transport. Cell Rep. 2017;21(4):1021–35. https://doi.org/10.1016/j.celrep.2017.09.091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. International journal of molecular sciences. 2018;19(11):3342. https://doi.org/10.3390/ijms19113342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ferré P, Foufelle F. SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Hormone Research in Paediatrics. 2007;68(2):72–82. https://doi.org/10.1159/000100426.

    Article  CAS  Google Scholar 

  24. Shimomura I, Bashmakov Y, Ikemoto S, Horton J, Brown M, Goldstein J. Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. PNAS. 1999;96:13656–61. https://doi.org/10.1073/pnas.96.24.13656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sewter C, Berger D, Considine RV, Medina G, Rochford J, Ciaraldi T, et al. Human obesity and type 2 diabetes are associated with alterations in SREBP1 isoform expression that are reproduced ex vivo by tumor necrosis factor-alpha. Diabetes. 2002;51(4):1035–41. https://doi.org/10.2337/diabetes.51.4.1035.

    Article  CAS  PubMed  Google Scholar 

  26. Lappas M. Effect of pre-existing maternal obesity, gestational diabetes and adipokines on the expression of genes involved in lipid metabolism in adipose tissue. Metabolism. 2014;63(2):250–62. https://doi.org/10.1016/j.metabol.2013.10.001.

    Article  CAS  PubMed  Google Scholar 

  27. Fatima SS, Khalid E, Ladak AA, Ali SA. Colostrum and mature breast milk analysis of serum irisin and sterol regulatory element-binding proteins-1c in gestational diabetes mellitus. J Matern Fetal Neonatal Med. 2019;32(18):2993–9. https://doi.org/10.1080/14767058.2018.1454422.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

The authors would like to thank the Necmettin Erbakan University for funding this project.

Funding

This work was supported by the Necmettin Erbakan University Scientific Research Projects Coordinator under Grant Number 191318004.

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Authors and Affiliations

  1. Department of Biochemistry, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Nurgul Eroglu

  2. Department of Biochemistry, Faculty of Medicine, Selcuk University, Alaaddin Keykubat Campus 42075 Selcuklu, Konya, Turkey

    Fatma Humeyra Yerlikaya & Duygu Eryavuz Onmaz

  3. Department of Obstetrics and Gynecology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Mehmet Cengiz Colakoglu

Authors
  1. Nurgul Eroglu
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  2. Fatma Humeyra Yerlikaya
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  3. Duygu Eryavuz Onmaz
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  4. Mehmet Cengiz Colakoglu
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Contributions

Conceptualization, funding acquisition, and project administration: F Humeyra Yerlikaya. Data curation, software, writing (original draft), and writing (review and editing): Duygu Eryavuz Onmaz. Formal analysis: Mehmet Cengiz Colakoglu. Investigation and writing (original draft): Nurgul Eroglu. All authors had final approval of the submitted and published versions.

Corresponding author

Correspondence to Duygu Eryavuz Onmaz.

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Ethics approval

The study was approved by the Necmettin Erbakan University Ethics Committee (Number: 2019/1700, Date: 08/02/2019) and was conducted in accordance with the Principles of Good Clinical Practice and the Declaration of Helsinki.

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The authors declare no competing interests.

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Written informed consent was obtained from all participants.

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Eroglu, N., Yerlikaya, F.H., Onmaz, D.E. et al. Role of ChREBP and SREBP-1c in gestational diabetes: two key players in glucose and lipid metabolism. Int J Diabetes Dev Ctries 43, 587–591 (2023). https://doi.org/10.1007/s13410-022-01050-x

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  • DOI: https://doi.org/10.1007/s13410-022-01050-x

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