Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Role of glucocorticoids in the physiopathology of excessive fat deposition and insulin resistance

International Journal of Obesity volume 28, pages S45–S52 (2004)Cite this article

Abstract

Glucocorticoids are important hormones in the regulation of metabolic homeostasis. We infused normal rats with dexamethasone given intracerebroventricularly (i.c.v.) for 3 days. This resulted in hyperphagia, hyperinsulinemia, and marked insulin resistance. Similar metabolic defects were observed following i.c.v. infusion of neuropeptide Y (NPY) in normal rats. As central dexamethasone infusion enhanced NPY content in the arcuate nucleus, it suggested that its metabolic effects are mediated by NPY. Moreover, due to the lack of effects observed in vagotomized animals, activation of the parasympathetic nervous system by central dexamethasone infusion is proposed. Glucocorticoid action is known to involve prereceptor metabolism by enzymes such as 11β-HSD-1 that converts inactive into active glucocorticoids. Mice overexpressing 11β-HSD-1 in adipose tissue were shown to be obese and insulin resistant. We recently observed that adipose tissue 11β-HSD-1 mRNA expression is increased at the onset of high-fat diet-induced obesity and positively correlated with the degree of hyperglycemia. In human obesity, increased adipose tissue 11β-HSD-1 expression and activity were also reported. Resistin is a new adipose tissue-secreted hormone shown to play a role in glucose homeostasis by increasing hepatic glucose production and inhibiting muscle and adipose tissue glucose utilization. We observed increased adipose tissue resistin expression in the early phase of high-fat diet-induced obesity as well as decreased resistin expression in response to leptin. A positive correlation between glycemia and adipose tissue resistin expression further suggested a role of this hormone in the development of insulin resistance. The melanocortin system is another important player in the regulation of energy balance. Peripheral administration of a melanocortin agonist decreased food intake and body weight and favored lipid oxidation, effects that were more marked in obese than in lean rats. It is proposed that both resistin and melanocortin agonists may influence adipose tissue 11β-HSD-1, thereby decreasing or enhancing glucose metabolism.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG . Central nervous system control of food intake. Nature 2000; 404: 661–671.

    CAS  PubMed  Google Scholar 

  2. Rohner-Jeanrenaud F . Aspects of the neuroendocrine regulation of body weight homeostasis. Ann Endocrinol (Paris) 2002; 63: 125–128.

    CAS  Google Scholar 

  3. Niswender KD, Schwartz MW . Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities. Front Neuroendocrinol 2003; 24: 1–10.

    CAS  PubMed  Google Scholar 

  4. Muccioli G, Tschop M, Papotti M, Deghenghi R, Heiman M, Ghigo E . Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity. Eur J Pharmacol 2002; 440: 235–254.

    CAS  PubMed  Google Scholar 

  5. Plotsky PM, Thrivikraman KV, Watts AG, Hauger RL . Hypothalamic–pituitary–adrenal axis function in the Zucker obese rat. Endocrinology 1992; 130: 1931–1941.

    CAS  PubMed  Google Scholar 

  6. Walker CD, Scribner KA, Stern JS, Dallman MF . Obese Zucker (fa/fa) rats exhibit normal target sensitivity to corticosterone and increased drive to adrenocorticotropin during the diurnal trough. Endocrinology 1992; 131: 2629–2637.

    CAS  PubMed  Google Scholar 

  7. Pacak K, McCarty R, Palkovits M, Cizza G, Kopin IJ, Goldstein DS, Chrousos GP . Decreased central and peripheral catecholaminergic activation in obese Zucker rats. Endocrinology 1995; 136: 4360–4367.

    CAS  PubMed  Google Scholar 

  8. Havel PJ, Busch BL, Curry DL, Johnson PR, Dallman MF, Stern JS . Predominately glucocorticoid agonist actions of RU-486 in young specific-pathogen-free Zucker rats. Am J Physiol 1996; 271: R710–R717.

    CAS  PubMed  Google Scholar 

  9. Richard D, Rivest R, Naimi N, Timofeeva E, Rivest S . Expression of corticotropin-releasing factor and its receptors in the brain of lean and obese Zucker rats. Endocrinology 1996; 137: 4786–4795.

    CAS  PubMed  Google Scholar 

  10. Timofeeva E, Richard D . Functional activation of CRH neurons and expression of the genes encoding CRH and its receptors in food-deprived lean (Fa/?) and obese (fa/fa) Zucker rats. Neuroendocrinology 1997; 66: 327–340.

    CAS  PubMed  Google Scholar 

  11. Timofeeva E, Deshaies Y, Picard F, Richard D . Corticotropin-releasing hormone-binding protein in brain and pituitary of food-deprived obese (fa/fa) Zucker rats. Am J Physiol 1999; 277: R1749–R1759.

    CAS  PubMed  Google Scholar 

  12. Livingstone DE, Jones GC, Smith K, Jamieson PM, Andrew R, Kenyon CJ, Walker BR . Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. Endocrinology 2000; 141: 560–563.

    CAS  PubMed  Google Scholar 

  13. Livingstone DE, Kenyon CJ, Walker BR . Mechanisms of dysregulation of 11 beta-hydroxysteroid dehydrogenase type 1 in obese Zucker rats. J Endocrinol 2000; 167: 533–539.

    CAS  PubMed  Google Scholar 

  14. Cunningham JJ, Calles-Escandon J, Garrido F, Carr DB, Bode HH . Hypercorticosteronuria and diminished pituitary responsiveness to corticotropin-releasing factor in obese Zucker rats. Endocrinology 1986; 118: 98–101.

    CAS  PubMed  Google Scholar 

  15. White BD, Corll CB, Porter JR . The metabolic clearance rate of corticosterone in lean and obese male Zucker rats. Metabolism 1989; 38: 530–536.

    CAS  PubMed  Google Scholar 

  16. Mattsson C, Lai M, Noble J, McKinney E, Yau JL, Seckl JR, Walker BR . Obese Zucker rats have reduced mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 1 expression in hippocampus-implications for dysregulation of the hypothalamic–pituitary–adrenal axis in obesity. Endocrinology 2003; 144: 2997–3003.

    CAS  PubMed  Google Scholar 

  17. Andrew R, Phillips DI, Walker BR . Obesity and gender influence cortisol secretion and metabolism in man. J Clin Endocrinol Metab 1998; 83: 1806–1809.

    CAS  PubMed  Google Scholar 

  18. Fraser R, Ingram MC, Anderson NH, Morrison C, Davies E, Connell JM . Cortisol effects on body mass, blood pressure, and cholesterol in the general population. Hypertension 1999; 33: 1364–1368.

    CAS  PubMed  Google Scholar 

  19. Stewart PM, Boulton A, Kumar S, Clark PM, Shackleton CH . Cortisol metabolism in human obesity: impaired cortisone → cortisol conversion in subjects with central adiposity. J Clin Endocrinol Metab 1999; 84: 1022–1027.

    CAS  PubMed  Google Scholar 

  20. Pasquali R, Gagliardi L, Vicennati V, Gambineri A, Colitta D, Ceroni L, Casimirri F . ACTH and cortisol response to combined corticotropin releasing hormone–arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome. Int J Obes Relat Metab Disord 1999; 23: 419–424.

    CAS  PubMed  Google Scholar 

  21. Pasquali R, Vicennati V, Calzoni F, Gnudi U, Gambineri A, Ceroni L, Cortelli P, Menozzi R, Sinisi R, Rio GD . alpha2-adrenoceptor regulation of the hypothalamic–pituitary–adrenocortical axis in obesity. Clin Endocrinol (Oxford) 2000; 52: 413–421.

    CAS  Google Scholar 

  22. Marin P, Darin N, Amemiya T, Andersson B, Jern S, Bjorntorp P . Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism 1992; 41: 882–886.

    CAS  PubMed  Google Scholar 

  23. Hautanen A, Adlercreutz H . Altered adrenocorticotropin and cortisol secretion in abdominal obesity: implications for the insulin resistance syndrome. J Intern Med 1993; 234: 461–469.

    CAS  PubMed  Google Scholar 

  24. Rosmond R, Dallman MF, Bjorntorp P . Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 1998; 83: 1853–1859.

    CAS  PubMed  Google Scholar 

  25. Ljung T, Andersson B, Bengtsson BA, Bjorntorp P, Marin P . Inhibition of cortisol secretion by dexamethasone in relation to body fat distribution: a dose–response study. Obes Res 1996; 4: 277–282.

    CAS  PubMed  Google Scholar 

  26. Jessop DS, Dallman MF, Fleming D, Lightman SL . Resistance to glucocorticoid feedback in obesity. J Clin Endocrinol Metab 2001; 86: 4109–4114.

    CAS  PubMed  Google Scholar 

  27. Di Blasio AM, van Rossum EF, Maestrini S, Berselli ME, Tagliaferri M, Podesta F, Koper JW, Liuzzi A, Lamberts SW . The relation between two polymorphisms in the glucocorticoid receptor gene and body mass index, blood pressure and cholesterol in obese patients. Clin Endocrinol (Oxford) 2003; 59: 68–74.

    CAS  Google Scholar 

  28. Reynolds RM, Chapman KE, Seckl JR, Walker BR, McKeigue PM, Lithell HO . Skeletal muscle glucocorticoid receptor density and insulin resistance. JAMA 2002; 287: 2505–2506.

    CAS  PubMed  Google Scholar 

  29. Whorwood CB, Donovan SJ, Flanagan D, Phillips DI, Byrne CD . Increased glucocorticoid receptor expression in human skeletal muscle cells may contribute to the pathogenesis of the metabolic syndrome. Diabetes 2002; 51: 1066–1075.

    CAS  PubMed  Google Scholar 

  30. Shimomura Y, Bray GA, Lee M . Adrenalectomy and steroid treatment in obese (ob/ob) and diabetic (db/db) mice. Horm Metab Res 1987; 19: 295–299.

    CAS  PubMed  Google Scholar 

  31. Zakrzewska KE, Cusin I, Stricker-Krongrad A, Boss O, Ricquier D, Jeanrenaud B, Rohner-Jeanrenaud F . Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat. Diabetes 1999; 48: 365–370.

    CAS  PubMed  Google Scholar 

  32. Cusin I, Rouru J, Rohner-Jeanrenaud F . Intracerebroventricular glucocorticoid infusion in normal rats: induction of parasympathetic-mediated obesity and insulin resistance. Obes Res 2001; 9: 401–406.

    CAS  PubMed  Google Scholar 

  33. Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B . Chronic intracerebroventricular neuropeptide-Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 1993; 133: 1753–1758.

    CAS  PubMed  Google Scholar 

  34. Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B . Intracerebroventricular administration of neuropeptide Y to normal rats has divergent effects on glucose utilization by adipose tissue and skeletal muscle. Diabetes 1994; 43: 764–769.

    CAS  PubMed  Google Scholar 

  35. Sainsbury A, Rohner-Jeanrenaud F, Grouzmann E, Jeanrenaud B . Acute intracerebroventricular administration of neuropeptide Y stimulates corticosterone output and feeding but not insulin output in normal rats. Neuroendocrinology 1996; 63: 318–326.

    CAS  PubMed  Google Scholar 

  36. Sainsbury A, Cusin I, Rohner-Jeanrenaud F, Jeanrenaud B . Adrenalectomy prevents the obesity syndrome produced by chronic central neuropeptide Y infusion in normal rats. Diabetes 1997; 46: 209–214.

    CAS  PubMed  Google Scholar 

  37. Zakrzewska KE, Sainsbury A, Cusin I, Rouru J, Jeanrenaud B, Rohner-Jeanrenaud F . Selective dependence of intracerebroventricular neuropeptide Y-elicited effects on central glucocorticoids. Endocrinology 1999; 140: 3183–3187.

    CAS  PubMed  Google Scholar 

  38. Seckl JR, Morton NM, Chapman KE, Walker BR . Glucocorticoids and 11beta-hydroxysteroid dehydrogenase in adipose tissue. Recent Prog Horm Res 2004; 59: 359–393.

    CAS  PubMed  Google Scholar 

  39. Moisan MP, Seckl JR, Edwards CR . 11 beta-hydroxysteroid dehydrogenase bioactivity and messenger RNA expression in rat forebrain: localization in hypothalamus, hippocampus, and cortex. Endocrinology 1990; 127: 1450–1455.

    CAS  PubMed  Google Scholar 

  40. Lakshmi V, Sakai RR, McEwen BS, Monder C . Regional distribution of 11 beta-hydroxysteroid dehydrogenase in rat brain. Endocrinology 1991; 128: 1741–1748.

    CAS  PubMed  Google Scholar 

  41. Seckl JR, Dow RC, Low SC, Edwards CR, Fink G . The 11 beta-hydroxysteroid dehydrogenase inhibitor glycyrrhetinic acid affects corticosteroid feedback regulation of hypothalamic corticotrophin-releasing peptides in rats. J Endocrinol 1993; 136: 471–477.

    CAS  PubMed  Google Scholar 

  42. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS . Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme. Mol Cell Endocrinol 1994; 105: R11–R17.

    CAS  PubMed  Google Scholar 

  43. Brown RW, Chapman KE, Kotelevtsev Y, Yau JL, Lindsay RS, Brett L, Leckie C, Murad P, Lyons V, Mullins JJ, Edwards CR, Seckl JR . Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2. Biochem J 1996; 313 (Part 3): 1007–1017.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Kotelevtsev Y, Holmes MC, Burchell A, Houston PM, Schmoll D, Jamieson P, Best R, Brown R, Edwards CR, Seckl JR, Mullins JJ . 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.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  46. Masuzaki H, Yamamoto H, Kenyon CJ, Elmquist JK, Morton NM, Paterson JM, Shinyama H, Sharp MG, Fleming S, Mullins JJ, Seckl JR, Flier JS . Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. J Clin Invest 2003; 112: 83–90.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  48. Rask E, Walker BR, Soderberg S, Livingstone DE, Eliasson M, Johnson O, Andrew R, Olsson T . 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 

  49. 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 

  50. Lindsay RS, Wake DJ, Nair S, Bunt J, Livingstone DE, Permana PA, Tataranni PA, Walker BR . Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians. J Clin Endocrinol Metab 2003; 88: 2738–2744.

    CAS  PubMed  Google Scholar 

  51. 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.

    CAS  PubMed  Google Scholar 

  52. Westerbacka J, Yki-Jarvinen H, Vehkavaara S, Hakkinen AM, Andrew R, Wake DJ, Seckl JR, Walker BR . Body fat distribution and cortisol metabolism in healthy men: enhanced 5beta-reductase and lower cortisol/cortisone metabolite ratios in men with fatty liver. J Clin Endocrinol Metab 2003; 88: 4924–4931.

    CAS  PubMed  Google Scholar 

  53. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA . The hormone resistin links obesity to diabetes. Nature 2001; 409: 307–312.

    CAS  PubMed  Google Scholar 

  54. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA . An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 1995; 270: 12953–12956.

    CAS  PubMed  Google Scholar 

  55. Day C . Thiazolidinediones: a new class of antidiabetic drugs. Diabet Med 1999; 16: 179–192.

    CAS  PubMed  Google Scholar 

  56. Reginato MJ, Lazar MA . Mechanisms by which thiazolidinediones enhance insulin action. Trends Endocrinol Metab 1999; 10: 9–13.

    CAS  PubMed  Google Scholar 

  57. Kim KH, Lee K, Moon YS, Sul HS . A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 2001; 276: 11252–11256.

    CAS  PubMed  Google Scholar 

  58. Holcomb IN, Kabakoff RC, Chan B, Baker TW, Gurney A, Henzel W, Nelson C, Lowman HB, Wright BD, Skelton NJ, Frantz GD, Tumas DB, Peale Jr FV, Shelton DL, Hebert CC . FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO J 2000; 19: 4046–4055.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Steppan CM, Brown EJ, Wright CM, Bhat S, Banerjee RR, Dai CY, Enders GH, Silberg DG, Wen X, Wu GD, Lazar MA . A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci USA 2001; 98: 502–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Morash BA, Willkinson D, Ur E, Wilkinson M . Resistin expression and regulation in mouse pituitary. FEBS Lett 2002; 526: 26–30.

    CAS  PubMed  Google Scholar 

  61. Nogueiras R, Gallego R, Gualillo O, Caminos JE, Garcia-Caballero T, Casanueva FF, Dieguez C . Resistin is expressed in different rat tissues and is regulated in a tissue- and gender-specific manner. FEBS Lett 2003; 548: 21–27.

    CAS  PubMed  Google Scholar 

  62. Haugen F, Jorgensen A, Drevon CA, Trayhurn P . Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett 2001; 507: 105–108.

    CAS  PubMed  Google Scholar 

  63. Del Arco A, Peralta S, Carrascosa JM, Ros M, Andres A, Arribas C . Alternative splicing generates a novel non-secretable resistin isoform in Wistar rats. FEBS Lett 2003; 555: 243–249.

    CAS  PubMed  Google Scholar 

  64. Rajala MW, Obici S, Scherer PE, Rossetti L . Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. J Clin Invest 2003; 111: 225–230.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Pravenec M, Kazdova L, Landa V, Zidek V, Mlejnek P, Jansa P, Wang J, Qi N, Kurtz TW . Transgenic and recombinant resistin impair skeletal muscle glucose metabolism in the spontaneously hypertensive rat. J Biol Chem 2003; 278: 45209–45215.

    CAS  PubMed  Google Scholar 

  66. Moon B, Kwan JJ, Duddy N, Sweeney G, Begum N . Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am J Physiol Endocrinol Metab 2003; 285: E106–E115.

    CAS  PubMed  Google Scholar 

  67. Yang RZ, Huang Q, Xu A, McLenithan JC, Eison JA, Shuldiner AR, Alkan S, Gong DW . Comparative studies of resistin expression and phylogenomics in human and mouse. Biochem Biophys Res Commun 2003; 310: 927–935.

    CAS  PubMed  Google Scholar 

  68. Kaser S, Kaser A, Sandhofer A, Ebenbichler CF, Tilg H, Patsch JR . Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun 2003; 309: 286–290.

    CAS  PubMed  Google Scholar 

  69. Raghu P, Ghosh S, Soundarya K, Haseeb A, Aruna B, Ehtesham NZ . Dimerization of human recombinant resistin involves covalent and noncovalent interactions. Biochem Biophys Res Commun 2004; 313: 642–646.

    CAS  PubMed  Google Scholar 

  70. Minn AH, Patterson NB, Pack S, Hoffmann SC, Gavrilova O, Vinson C, Harlan DM, Shalev A . Resistin is expressed in pancreatic islets. Biochem Biophys Res Commun 2003; 310: 641–645.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  72. 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.

    CAS  PubMed  Google Scholar 

  73. 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.

    CAS  PubMed  Google Scholar 

  74. Seow KM, Juan CC, Wu LY, Hsu YP, Yang WM, Tsai YL, Hwang JL, Ho LT . Serum and adipocyte resistin in polycystic ovary syndrome with insulin resistance. Hum Reprod 2004; 19: 48–53.

    CAS  PubMed  Google Scholar 

  75. Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, Watson W, Kerr K, Jones R, Zhu Q, Considine RV . Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 2003; 88: 5452–5455.

    CAS  PubMed  Google Scholar 

  76. Azuma K, Katsukawa F, Oguchi S, Murata M, Yamazaki H, Shimada A, Saruta T . Correlation between serum resistin level and adiposity in obese individuals. Obes Res 2003; 11: 997–1001.

    CAS  PubMed  Google Scholar 

  77. Youn BS, Yu KY, Park HJ, Lee NS, Min SS, Youn MY, Cho YM, Park YJ, Kim SY, Lee HK, Park KS . Plasma resistin concentrations measured by enzyme-linked immunosorbent assay using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 2004; 89: 150–156.

    CAS  PubMed  Google Scholar 

  78. McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S . Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 2003; 88: 6098–6106.

    CAS  PubMed  Google Scholar 

  79. Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ . Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003; 149: 331–335.

    CAS  PubMed  Google Scholar 

  80. Smith SR, Bai F, Charbonneau C, Janderova L, Argyropoulos G . A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. Diabetes 2003; 52: 1611–1618.

    CAS  PubMed  Google Scholar 

  81. McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S . Resistin, central obesity, and type 2 diabetes. Lancet 2002; 359: 46–47.

    CAS  PubMed  Google Scholar 

  82. McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S . Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 2002; 87: 2407.

    CAS  PubMed  Google Scholar 

  83. Asensio C, Cettour-Rose P, Theander-Carrillo C, Rohner-Jeanrenaud F, Muzzin P . Changes of glycemia by leptin administration or high fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis. Endocrinology 2004; 145: 2206–2213.

    CAS  PubMed  Google Scholar 

  84. Ellacott KL, Cone RD . The central melanocortin system and the integration of short- and long-term regulators of energy homeostasis. Recent Prog Horm Res 2004; 59: 395–408.

    CAS  PubMed  Google Scholar 

  85. Cettour-Rose P, Rohner-Jeanrenaud F . The leptin-like effects of 3-d peripheral administration of a melanocortin agonist are more marked in genetically obese Zucker (fa/fa) than in lean rats. Endocrinology 2002; 143: 2277–2283.

    CAS  PubMed  Google Scholar 

  86. Harrold JA, Widdowson PS, Williams G . Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. Diabetes 1999; 48: 267–271.

    CAS  PubMed  Google Scholar 

  87. Yaswen L, Diehl N, Brennan MB, Hochgeschwender U . Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 1999; 5: 1066–1070.

    CAS  PubMed  Google Scholar 

  88. Li G, Mobbs CV, Scarpace PJ . Central pro-opiomelanocortin gene delivery results in hypophagia, reduced visceral adiposity, and improved insulin sensitivity in genetically obese Zucker rats. Diabetes 2003; 52: 1951–1957.

    CAS  PubMed  Google Scholar 

  89. Vettor R, Zarjevski N, Cusin I, Rohner-Jeanrenaud F, Jeanrenaud B . Induction and reversibility of an obesity syndrome by intracerebroventricular neuropeptide Y administration to normal rats. Diabetologia 1994; 37: 1202–1208.

    CAS  PubMed  Google Scholar 

  90. Sainsbury A, Cusin I, Doyle P, Rohner-Jeanrenaud F, Jeanrenaud B . Intracerebroventricular administration of neuropeptide Y to normal rats increases obese gene expression in white adipose tissue. Diabetologia 1996; 39: 353–356.

    CAS  PubMed  Google Scholar 

  91. Sainsbury A, Rohner-Jeanrenaud F, Cusin I, Zakrzewska KE, Halban PA, Gaillard RC, Jeanrenaud B . Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia. Diabetologia 1997; 40: 1269–1277.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Department of Cell Biology and Metabolism, Laboratory of Metabolism, Faculty of Medicine, University of Geneva, Switzerland

    C Asensio & F Rohner-Jeanrenaud

  2. Department of Cell Biology and Metabolism, Faculty of Medicine, University of Geneva, Switzerland

    C Asensio & P Muzzin

Authors
  1. C Asensio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Muzzin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F Rohner-Jeanrenaud
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F Rohner-Jeanrenaud.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Asensio, C., Muzzin, P. & Rohner-Jeanrenaud, F. Role of glucocorticoids in the physiopathology of excessive fat deposition and insulin resistance. Int J Obes 28 (Suppl 4), S45–S52 (2004). https://doi.org/10.1038/sj.ijo.0802856

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802856

Keywords

This article is cited by

Search

Advanced search

Quick links