Vol 70, No 2 (2019)
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Published online: 2018-11-27

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Comparison of adipose tissue derived genes in endogenous Cushing’s syndrome versus diet-induced obesity

Judit Denes1, Adrienn Zsippai2, Laszlo Kovacs1, Zoltan Gorombey1, Gabor L. Kovacs3, Miklos Goth1, Peter Igaz2, Erika Hubina1
Pubmed: 30480750
Endokrynol Pol 2019;70(2):131-134.

Abstract

Introduction: Dysregulation of adipokine secretion and action is a characteristic feature of obesity and a key clinical feature of Cushing’s syndrome (CS). We have investigated whether endogenous glucocorticoid excess influences adipose tissue-derived gene expression.

Material and methods: mRNA expression of adipokines; adiponectin, resistin, tumour necrosis factor-a, interleukin-6 (IL-6), angiotensinogen (AGT), plasminogen activator inhibitor type 1, retinol binding protein 4, visfatin, and cystatin C was assessed by quantitative real-time RT-PCR in visceral adipose tissue removed during abdominal surgery of eight patients with CS, and six control patients.

Results: We did not find any significant difference in the investigated genes; however, the almost significant overexpression of AGT and underexpression of IL-6 might be noteworthy (p = 0.06 in both cases).

Conclusions: No significant differences were found in the expression of the investigated genes known as cardiometabolic risk factors. This indicates that there are no major differences between endogenous hypercortisolism or diet-induced obesity regarding the expression of adipokines involved in cardiometabolic disorders. However, the difference in AGT and IL-6 expression might be included in pathways affecting fat distribution in CS

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References

  1. Walker GE, Marzullo P, Ricotti R, et al. The pathophysiology of abdominal adipose tissue depots in health and disease. Horm Mol Biol Clin Investig. 2014; 19(1): 57–74.
  2. Dallman MF, Warne JP, Foster MT, et al. Glucocorticoids and insulin both modulate caloric intake through actions on the brain. J Physiol. 2007; 583(Pt 2): 431–436.
  3. Hauner H, Schmid P, Pfeiffer EF. Glucocorticoids and insulin promote the differentiation of human adipocyte precursor cells into fat cells. J Clin Endocrinol Metab. 1987; 64(4): 832–835.
  4. Lee MJ, Pramyothin P, Karastergiou K, et al. Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. Biochim Biophys Acta. 2014; 1842(3): 473–481.
  5. Valassi E, Biller BMK, Klibanski A, et al. Adipokines and cardiovascular risk in Cushing's syndrome. Neuroendocrinology. 2012; 95(3): 187–206.
  6. Hochberg I, Harvey I, Tran QT, et al. Gene expression changes in subcutaneous adipose tissue due to Cushing's disease. J Mol Endocrinol. 2015; 55(2): 81–94.
  7. Umemura S, Nyui N, Tamura K, et al. Plasma angiotensinogen concentrations in obese patients. Am J Hypertens. 1997; 10(6): 629–633.
  8. van Harmelen V, Elizalde M, Ariapart P, et al. The association of human adipose angiotensinogen gene expression with abdominal fat distribution in obesity. Int J Obes Relat Metab Disord. 2000; 24(6): 673–678.
  9. Lijnen HR. Angiogenesis and obesity. Cardiovasc Res. 2008; 78(2): 286–293.
  10. Cao Y. Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov. 2010; 9(2): 107–115.
  11. Vincent F, Bonnin P, Clemessy M, et al. Angiotensinogen delays angiogenesis and tumor growth of hepatocarcinoma in transgenic mice. Cancer Res. 2009; 69(7): 2853–2860.
  12. Corvol P, Lamandé N, Cruz A, et al. Inhibition of angiogenesis: a new function for angiotensinogen and des(angiotensin I)angiotensinogen. Curr Hypertens Rep. 2003; 5(2): 149–154.
  13. Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc. 2001; 60(3): 349–356.
  14. Barahona MJ, Sucunza N, Resmini E, et al. Persistent body fat mass and inflammatory marker increases after long-term cure of Cushing's syndrome. J Clin Endocrinol Metab. 2009; 94(9): 3365–3371.
  15. Papanicolaou DA, Tsigos C, Oldfield EH, et al. Acute glucocorticoid deficiency is associated with plasma elevations of interleukin-6: does the latter participate in the symptomatology of the steroid withdrawal syndrome and adrenal insufficiency? J Clin Endocrinol Metab. 1996; 81(6): 2303–2306.
  16. Górska R, Gregorek H, Kowalski J, et al. Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis. J Clin Periodontol. 2003; 30(12): 1046–1052.
  17. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998; 83(3): 847–850.
  18. Hoppmann J, Perwitz N, Meier B, et al. The balance between gluco- and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol. 2010; 204(2): 153–164.
  19. Erem C, Nuhoglu I, Yilmaz M, et al. Blood coagulation and fibrinolysis in patients with Cushing's syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels. J Endocrinol Invest. 2009; 32(2): 169–174.
  20. Patrassi GM, Sartori MT, Viero ML, et al. The fibrinolytic potential in patients with Cushing's disease: a clue to their hypercoagulable state. Blood Coagul Fibrinolysis. 1992; 3(6): 789–793.
  21. Fatti LM, Bottasso B, Invitti C, et al. Markers of activation of coagulation and fibrinolysis in patients with Cushing's syndrome. J Endocrinol Invest. 2000; 23(3): 145–150.
  22. Moraes-Vieira PM, Yore MM, Dwyer PM, et al. RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance. Cell Metab. 2014; 19(3): 512–526.
  23. Lee MJ, Gong DW, Burkey BF, et al. Pathways regulated by glucocorticoids in omental and subcutaneous human adipose tissues: a microarray study. Am J Physiol Endocrinol Metab. 2011; 300(3): E571–E580.
  24. Fallo F, Scarda A, Sonino N, et al. Effect of glucocorticoids on adiponectin: a study in healthy subjects and in Cushing's syndrome. Eur J Endocrinol. 2004; 150(3): 339–344.
  25. Libè R, Morpurgo PS, Cappiello V, et al. Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery. Clin Endocrinol (Oxf). 2005; 62(1): 30–36.
  26. Krsek M, Silha JV, Jezková J, et al. Adipokine levels in Cushing's syndrome; elevated resistin levels in female patients with Cushing's syndrome. Clin Endocrinol (Oxf). 2004; 60(3): 350–357.
  27. Klaasen R, Herenius MMJ, Wijbrandts CA, et al. Treatment-specific changes in circulating adipocytokines: a comparison between tumour necrosis factor blockade and glucocorticoid treatment for rheumatoid arthritis. Ann Rheum Dis. 2012; 71(9): 1510–1516.
  28. Fried SK, Russell CD, Grauso NL, et al. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. J Clin Invest. 1993; 92(5): 2191–2198.
  29. Russell CD, Petersen RN, Rao SP, et al. Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone. Am J Physiol. 1998; 275(3 Pt 1): E507–E515.
  30. Kola B, Christ-Crain M, Lolli F, et al. Changes in adenosine 5'-monophosphate-activated protein kinase as a mechanism of visceral obesity in Cushing's syndrome. J Clin Endocrinol Metab. 2008; 93(12): 4969–4973.
  31. Bujalska IJ, Kumar S, Stewart PM. Does central obesity reflect "Cushing's disease of the omentum"? Lancet. 1997; 349(9060): 1210–1213.