Journal of Animal Science and Technology

Korean Society of Animal Sciences and Technology (한국축산학회)
권호 표지
DOI QR코드

DOI QR Code

Intrauterine diabetic milieu instigates dysregulated adipocytokines production in F1 offspring

  • Tawfik, Shady H. (Department of Biochemistry, Medical Research Institute, Alexandria University) ;
  • Haiba, Maha M. (Department of Biochemistry, Medical Research Institute, Alexandria University) ;
  • Saad, Mohamed I. (Department of Biochemistry, Medical Research Institute, Alexandria University) ;
  • Abdelkhalek, Taha M. (Department of Human Genetics, Medical Research Institute, Alexandria University) ;
  • Hanafi, Mervat Y. (Department of Biochemistry, Medical Research Institute, Alexandria University) ;
  • Kamel, Maher A. (Department of Biochemistry, Medical Research Institute, Alexandria University)
  • Received : 2016.08.10
  • Accepted : 2016.12.02
  • Published : 2017.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Intrauterine environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome. Diabetes is associated with low-grade inflammatory state and dysregulated adipokines production. The aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-${\alpha}$) production in F1 offspring in rats. Methods: The offspring groups were as follows: F1 offspring of control mothers under control diet (CD) (CF1-CD), F1 offspring of control mothers under high caloric diet (HCD) (CF1-HCD), F1 offspring of diabetic mothers under CD (DF1-CD), and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks post-natal, 10 pups of each subgroup were culled to obtain blood samples for biochemical analysis. Results: The results indicate that DF1-CD and DF1-HCD groups exhibited hyperinsulinemia, dyslipidemia, insulin resistance and impaired glucose homeostasis compared to CF1-CD (p > 0.05). DF1-CD and DF1-HCD groups had high hepatic and muscular depositions of TGs. The significant elevated NEFA level only appeared in offspring of diabetic mothers that was fed HCD. DF1-CD and DF1-HCD groups demonstrated low serum levels of adiponectin, high levels of leptin, and elevated levels of TNF-${\alpha}$ compared to CF1-CD (p > 0.05). These results reveal the disturbed metabolic lipid profile of offspring of diabetic mothers and could guide further characterization of the mechanisms involved. Conclusion: Dysregulated adipocytokines production could be a possible mechanism for the transgenerational transmittance of diabetes, especially following a postnatal diabetogenic environment. Moreover, the exacerbating effects of postnatal HCD on NEFA in rats might be prone to adipcytokine dysregulation. Furthermore, dysregulation of serum adipokines is a prevalent consequence of maternal diabetes and could guide further investigations to predict the development of metabolic disturbances.

Keywords

References

  1. Gluckman PD, Hanson MA. The developmental origins of the metabolic syndrome. Trends Endocrinol Metab. 2004;15(4):183-7. https://doi.org/10.1016/j.tem.2004.03.002
  2. Aerts L, Van Assche FA. Animal evidence for the transgenerational development of diabetes mellitus. Int J Biochem Cell Biol. 2006;38(5):894-903. https://doi.org/10.1016/j.biocel.2005.07.006
  3. Fowden AL, Giussani DA, Forhead AJ. Intrauterine programming of physiological systems: causes and consequences. Physiology. 2006;21(1):29-37. https://doi.org/10.1152/physiol.00050.2005
  4. Saad MI, Abdelkhalek TM, Saleh MM, Kamel MA, Youssef M, Tawfik SH, Dominguez H. Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells. Endocrine. 2015;50(537):1-31. doi:10.1007/s12020-015-0709-4.
  5. Saad MI, Kamel MA, Hanafi MY. Modulation of adipocytokines production and serum NEFA level by metformin, glimepiride, and sitagliptin in HFD/STZ diabetic rats. Biochem Res Int. 2015.
  6. Tawfik SH, Mahmoud BF, Saad MI, Shehata M, Kamel MA, Helmy MH. Similar and additive effects of ovariectomy and diabetes on insulin resistance and lipid metabolism. Biochem Res Int. 2015.
  7. Zorena K, Mysliwska J, Mysliwiec M, Balcerska A, Lipowski P, Raczynska K. Relationship between serum levels of tumor necrosis factor-alpha and interleukin-6 in diabetes mellitus type 1 children. Cen Eur J Immunol. 2007;32(3):124.
  8. Makino N, Maeda T, Sugano M, Satoh S, Watanabe R, Abe N. High serum $TNF-{\alpha}$ level in Type 2 diabetic patients with microangiopathy is associated with eNOS down-regulation and apoptosis in endothelial cells. J Diabetes Complicat. 2005;19(6):347-55. https://doi.org/10.1016/j.jdiacomp.2005.04.002
  9. Liguori A, Puglianiello A, Germani D, Deodati A, Peschiaroli E, Cianfarani S. Epigenetic changes predisposing to type 2 diabetes in intrauterine growth retardation. Front Endocrinol. 2010;1
  10. Reusens B, Remacle C. Programming of the endocrine pancreas by the early nutritional environment. Int J Biochem Cell Biol. 2006;38(5):913-22. https://doi.org/10.1016/j.biocel.2005.10.012
  11. Kamel MA. Prenatal effects of different intra-uterine milieus on fetal glucose sensing mechanisms during gestation in rats. 2012. Journal of Diabetes & Metabolism.
  12. Kanaka‐Gantenbein C. Fetal origins of adult diabetes. Ann N Y Acad Sci. 2010;1205(1):99-105. https://doi.org/10.1111/j.1749-6632.2010.05683.x
  13. Mooradian AD. Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5(3):150-9. https://doi.org/10.1038/ncpendmet1066
  14. Delarue J, Magnan C. Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care. 2007;10(2):142-8. https://doi.org/10.1097/MCO.0b013e328042ba90
  15. Boden G, Shulman G. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and $\beta$‐cell dysfunction. Eur J Clin Investig. 2002;32(s3):14-23. https://doi.org/10.1046/j.1365-2362.32.s3.3.x
  16. Steneberg P, Sykaras AG, Backlund F, Straseviciene J, Soderstrom I, Edlund H. Hyperinsulinemia enhances hepatic expression of the fatty acid transporter Cd36 and provokes hepatosteatosis and hepatic insulin resistance. J Biol Chem. 2015;290(31):19034-43. https://doi.org/10.1074/jbc.M115.640292
  17. Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Investig. 2005;115(12):3587. https://doi.org/10.1172/JCI25151
  18. Hosokawa Y, Yamada Y, Obata Y, Baden MY, Saisho K, Ihara A, Yamamoto K, Katsuragi K, Matsuzawa Y. Clinical significance of serum adiponectin in Japanese diabetic patients. Diabetol Int. 2011;2(2):65-71. https://doi.org/10.1007/s13340-011-0027-x
  19. Ruotsalainen E, Vauhkonen I, Salmenniemi U, Pihlajamaki J, Punnonen K, Kainulainen S, Jalkanen S, Salmi M, Laakso M. Markers of endothelial dysfunction and low-grade inflammation are associated in the offspring of type 2 diabetic subjects. Atherosclerosis. 2008;197(1):271-7. https://doi.org/10.1016/j.atherosclerosis.2007.04.021
  20. Ruotsalainen E, Salmenniemi U, Vauhkonen I, Pihlajamaki J, Punnonen K, Kainulainen S, Laakso M. Changes in inflammatory cytokines are related to impaired glucose tolerance in offspring of type 2 diabetic subjects. Diabetes Care. 2006;29(12):2714-20. https://doi.org/10.2337/dc06-0147
  21. Maltezos E, Papazoglou D, Exiara T, Papazoglou L, Karathanasis E, Christakidis D, Ktenidou-Kartali S. Tumour necrosis factor-$\alpha$ levels in non-diabetic offspring of patients with type 2 diabetes mellitus. J Int Med Res. 2002;30(6):576-83. https://doi.org/10.1177/147323000203000605
  22. Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004;25(1):4-7. https://doi.org/10.1016/j.it.2003.10.013
  23. Yamakawa I, Kojima H, Terashima T, Katagi M, Oi J, Urabe H, Sanada M, Kawai H, Chan L, Yasuda H. Inactivation of $TNF-{\alpha}$ ameliorates diabetic neuropathy in mice. Am J Physiol-Endocrinol Metab. 2011;301(5):E844-52. https://doi.org/10.1152/ajpendo.00029.2011

Cited by

  1. Maternal High-Fat Diet Disturbs the DNA Methylation Profile in the Brown Adipose Tissue of Offspring Mice vol.12, pp.None, 2021, https://doi.org/10.3389/fendo.2021.705827