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Depot-specific messenger RNA expression of 11β-hydroxysteroid dehydrogenase type 1 and leptin in adipose tissue of children and adults

International Journal of Obesity volume 31, pages 820–828 (2007)Cite this article

Abstract

Objective:

To compare expression of messenger RNA (mRNA) coding for the cortisol regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), and the adipocytokines leptin and resistin in paired biopsies of subcutaneous adipose tissue (SC) and omental adipose tissue (OM) from children.

Design:

Paired biopsies (SC and OM) were obtained from 54 children (age 0.17–16 years, body mass index (BMI) 12.5–28.3 kg/m2, BMI standard deviation score (SDS) −2.5–4.5) and 16 adults (age 27–79 years, BMI 19–46 kg/m2) undergoing open abdominal surgery. mRNA levels of 11β-HSD1, leptin and resistin were measured using quantitative real-time polymerase chain reaction (PCR).

Results:

11β-HSD1 mRNA level was higher in OM than in SC (P<0.05), whereas leptin mRNA was higher in SC than in OM (P<0.001). There was no difference in the resistin mRNA level between SC and OM. These results were consistent in children and adults. In children, 11β-HSD1 mRNA in SC was positively associated with BMI SDS (P<0.05), whereas in OM it was positively associated with age (P<0.05). The association between 11β-HSD1 expression and age remained significant after adjustment for BMI SDS and gender. Leptin mRNA was positively associated with BMI SDS (SC: P<0.001, OM: P<0.001) but not with age in children. In multiple regression analyses, including anthropometric variables and age, BMI SDS was independently associated with mRNA levels of 11β-HSD1 (P<0.05) and leptin (P<0.001) in SC. When normal weight and overweight children were analyzed separately, 11β-HSD1 mRNA levels were positively associated with leptin in OM in the overweight group (P<0.05).

Conclusion:

There are depot-specific differences in mRNA levels of 11β-HSD1 and leptin in children and adults. The positive association of 11β-HSD1 mRNA in OM with age may reflect a causal role in visceral fat accumulation during growth. Increasing 11β-HSD1 and leptin mRNA in SC with increasing BMI SDS could suggest that the risk of metabolic consequences of obesity may be established early in life.

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References

  1. Goran MI, Ball GD, Cruz ML . Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab 2003; 88: 1417–1427.

    Article  CAS  Google Scholar 

  2. Power C, Lake JK, Cole TJ . Measurement and long-term health risks of child and adolescent fatness. Int J Obes Relat Metab Disord 1997; 21: 507–526.

    Article  CAS  Google Scholar 

  3. Dietz WH . Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics 1998; 101: 518–525.

    CAS  Google Scholar 

  4. Dietz WH . Childhood weight affects adult morbidity and mortality. J Nutr 1998; 128: 411S–414S.

    Article  CAS  Google Scholar 

  5. Steinberger J . Diagnosis of the metabolic syndrome in children. Curr Opin Lipidol 2003; 14: 555–559.

    Article  CAS  Google Scholar 

  6. Sinha R, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002; 346: 802–810.

    Article  CAS  Google Scholar 

  7. Goran MI . Visceral fat in prepubertal children: Influence of obesity, anthropometry, ethnicity, gender, diet, and growth. Am J Human Biol 1999; 11: 201–207.

    Article  Google Scholar 

  8. Montague CT, O’Rahilly S . The perils of portliness: causes and consequences of visceral adiposity. Diabetes 2000; 49: 883–888.

    Article  CAS  Google Scholar 

  9. Guerre-Millo M . Adipose tissue hormones. J Endocrinol Invest 2002; 25: 855–861.

    Article  CAS  Google Scholar 

  10. Flier JS . Obesity wars. Molecular progress confronts an expanding epidemic. Cell 2004; 116: 337–350.

    Article  CAS  Google Scholar 

  11. Pittas AG, Joseph NA, Greenberg AS . Adipocytokines and insulin resistance. J Clin Endocrinol Metab 2004; 89: 447–452.

    Article  CAS  Google Scholar 

  12. Bjorntorp P, Rosmond R . Obesity and cortisol. Nutrition 2000; 16: 924–936.

    Article  CAS  Google Scholar 

  13. Seckl JR, Walker BR . 11beta-hydroxysteroid dehydrogenase type 1 – a tissue-specific amplifier of glucocorticoid action. Endocrinology 2001; 142: 1371–1376.

    Article  CAS  Google Scholar 

  14. Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS et al. 11{beta}-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocrine Rev 2004; 25: 831–866.

    Article  CAS  Google Scholar 

  15. Rask E, Olsson T, Soderberg S, Andrew R, Livingstone DE, Johnson O et al. Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab 2001; 86: 1418–1421.

    Article  CAS  Google Scholar 

  16. Rask E, Walker BR, Soderberg S, Livingstone DE, Eliasson M, Johnson O et al. Tissue-specific changes in peripheral cortisol metabolism in obese women: increased adipose 11beta-hydroxysteroid dehydrogenase type 1 activity. J Clin Endocrinol Metab 2002; 87: 3330–3336.

    CAS  PubMed  Google Scholar 

  17. Wake DJ, Rask E, Livingstone DE, Soderberg S, Olsson T, Walker BR . Local and systemic impact of transcriptional up-regulation of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue in human obesity. J Clin Endocrinol Metab 2003; 88: 3983–3988.

    Article  CAS  Google Scholar 

  18. Paulmyer-Lacroix O, Boullu S, Oliver C, Alessi MC, Grino M . Expression of the mRNA coding for 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue from obese patients: an in situ hybridization study. J Clin Endocrinol Metab 2002; 87: 2701–2705.

    CAS  PubMed  Google Scholar 

  19. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR et al. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001; 294: 2166–2170.

    Article  CAS  Google Scholar 

  20. Masuzaki H, Yamamoto H, Kenyon CJ, Elmquist JK, Morton NM, Paterson JM et al. Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. J Clin Invest 2003; 112: 83–90.

    Article  CAS  Google Scholar 

  21. Kotelevtsev Y, Holmes MC, Burchell A, Houston PM, Schmoll D, Jamieson P et al. 11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proc Natl Acad Sci USA 1997; 94: 14924–14929.

    Article  CAS  Google Scholar 

  22. Wauters M, Considine RV, Van Gaal LF . Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 2000; 143: 293–311.

    Article  CAS  Google Scholar 

  23. Diez JJ, Iglesias P . The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 2003; 148: 293–300.

    Article  CAS  Google Scholar 

  24. Lofgren P, van Harmelen V, Reynisdottir S, Naslund E, Ryden M, Rossner S et al. Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue. Diabetes 2000; 49: 688–692.

    Article  CAS  Google Scholar 

  25. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM et al. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307–312.

    Article  CAS  Google Scholar 

  26. Fain JN, Bahouth SW, Madan AK . TNFalpha release by the nonfat cells of human adipose tissue. Int J Obes Relat Metab Disord 2004; 28: 616–622.

    Article  CAS  Google Scholar 

  27. Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV et al. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 2001; 50: 2199–2202.

    Article  CAS  Google Scholar 

  28. Fisher FM, McTernan PG, Valsamakis G, Chetty R, Harte AL, Anwar AJ et al. Differences in adiponectin protein expression: effect of fat depots and type 2 diabetic status. Horm Metab Res 2002; 34: 650–654.

    Article  CAS  Google Scholar 

  29. Montague CT, Prins JB, Sanders L, Zhang J, Sewter CP, Digby J et al. Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 1998; 47: 1384–1391.

    Article  CAS  Google Scholar 

  30. Dusserre E, Moulin P, Vidal H . Differences in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues. Biochim Biophys Acta 2000; 1500: 88–96.

    Article  CAS  Google Scholar 

  31. 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: 847–850.

    CAS  PubMed  Google Scholar 

  32. Russell CD, Petersen RN, Rao SP, Ricci MR, Prasad A, Zhang Y et al. Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone. Am J Physiol 1998; 275: E507–E515.

    CAS  PubMed  Google Scholar 

  33. Fasshauer M, Paschke R . Regulation of adipocytokines and insulin resistance. Diabetologia 2003; 46: 1594–1603.

    Article  CAS  Google Scholar 

  34. Fredriks AM, van Buuren S, Wit JM, Verloove-Vanhorick SP . Body index measurements in 1996–1997 compared with 1980. Arch Dis Child 2000; 82: 107–112.

    Article  CAS  Google Scholar 

  35. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH . Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000; 320: 1240–1243.

    Article  CAS  Google Scholar 

  36. de Onis M, Blossner M . Prevalence and trends of overweight among preschool children in developing countries. Am J Clin Nutr 2000; 72: 1032–1039.

    Article  CAS  Google Scholar 

  37. Bujalska IJ, Kumar S, Hewison M, Stewart PM . Differentiation of adipose stromal cells: the roles of glucocorticoids and 11beta-hydroxysteroid dehydrogenase. Endocrinology 1999; 140: 3188–3196.

    Article  CAS  Google Scholar 

  38. Tomlinson JW, Sinha B, Bujalska I, Hewison M, Stewart PM . Expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue is not increased in human obesity. J Clin Endocrinol Metab 2002; 87: 5630–5635.

    Article  CAS  Google Scholar 

  39. Bujalska IJ, Kumar S, Stewart PM . Does central obesity reflect ‘Cushing's disease of the omentum’? Lancet 1997; 349: 1210–1213.

    Article  CAS  Google Scholar 

  40. Bakker AH, Van Dielen FM, Greve JW, Adam JA, Buurman WA . Preadipocyte number in omental and subcutaneous adipose tissue of obese individuals. Obes Res 2004; 12: 488–498.

    Article  Google Scholar 

  41. Wellen KE, Hotamisligil GS . Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003; 112: 1785–1788.

    Article  CAS  Google Scholar 

  42. Tomlinson JW, Moore J, Cooper MS, Bujalska I, Shahmanesh M, Burt C et al. Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines. Endocrinology 2001; 142: 1982–1989.

    Article  CAS  Google Scholar 

  43. Boulton TJ, Dunlop M, Court JM . The growth and development of fat cells in infancy. Pediatr Res 1978; 12: 908–911.

    Article  CAS  Google Scholar 

  44. Kannisto K, Pietilainen KH, Ehrenborg E, Rissanen A, Kaprio J, Hamsten A et al. Overexpression of 11beta-hydroxysteroid dehydrogenase-1 in adipose tissue is associated with acquired obesity and features of insulin resistance: studies in young adult monozygotic twins. J Clin Endocrinol Metab 2004; 89: 4414–4421.

    Article  CAS  Google Scholar 

  45. Engeli S, Bohnke J, Feldpausch M, Gorzelniak K, Heintze U, Janke J et al. Regulation of 11beta-HSD genes in human adipose tissue: influence of central obesity and weight loss. Obes Res 2004; 12: 9–17.

    Article  CAS  Google Scholar 

  46. Soderberg S, Ahren B, Jansson JH, Johnson O, Hallmans G, Asplund K et al. Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999; 246: 409–418.

    Article  CAS  Google Scholar 

  47. Soderberg S, Stegmayr B, Stenlund H, Sjostrom LG, Agren A, Johansson L et al. Leptin, but not adiponectin, predicts stroke in males. J Intern Med 2004; 256: 128–136.

    Article  CAS  Google Scholar 

  48. Horbach T, Stohr W, Rascher W, Dotsch J . Comparison of leptin gene expression in different adipose tissues in children and adults. Eur J Endocrinol 2004; 150: 579–584.

    Article  Google Scholar 

  49. Nagaev I, Smith U . Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 2001; 285: 561–564.

    Article  CAS  Google Scholar 

  50. Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM . Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res 2002; 10: 1–5.

    Article  CAS  Google Scholar 

  51. Dimitriou T, Maser-Gluth C, Remer T . Adrenocortical activity in healthy children is associated with fat mass. Am J Clin Nutr 2003; 77: 731–736.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the Swedish Research Council to OH and TO and from the Health Bureau of Jiangsu Province (H200501). We thank Drs Yi Jun, Liu Jiyan (Nanjing Children's Hospital), Chen Yijiang (Department of Surgery, Nanjing Medical University), Professor Peter Naredi and Dr Toralph Ruge (Department of Surgical and Perioperative Sciences, Surgery, Umeå University) for providing adipose tissues biopsies. We thank Hans Stenlund for help in statistics.

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Authors and Affiliations

  1. Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden

    X Li, S Lindquist & O Hernell

  2. Children's Research Institute of Nanjing Medical University, Nanjing, China

    X Li & R Chen

  3. Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden

    T Myrnäs

  4. Department of Pediatric Surgery, University Children's Hospital, Uppsala, Sweden

    G Angsten

  5. Department of Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden

    T Olsson

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Correspondence to X Li.

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Li, X., Lindquist, S., Chen, R. et al. Depot-specific messenger RNA expression of 11β-hydroxysteroid dehydrogenase type 1 and leptin in adipose tissue of children and adults. Int J Obes 31, 820–828 (2007). https://doi.org/10.1038/sj.ijo.0803470

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