Horm Metab Res 2008; 40(8): 515-517
DOI: 10.1055/s-2008-1073154
Mini Review

© Georg Thieme Verlag KG Stuttgart · New York

Adrenocortical Dysfunction in Obesity and the Metabolic Syndrome

A. W. Krug 1 , M. Ehrhart-Bornstein 1
  • 1Carl Gustav Carus University Hospital, Department of Internal Medicine III, Dresden, Germany
Further Information

Publication History

received 28.09.2007

accepted 25.02.2008

Publication Date:
30 April 2008 (online)

Abstract

Recently, it has become evident that the adrenals play a key role in obesity as well as in the metabolic syndrome and their complications. On the one hand, adrenal steroids are involved in physiological regulation of adipose tissue and energy homeostasis and in the pathogenesis of cardiometabolic complications. On the other hand, fat cell-derived factors, adipocytokines, and lipids released from adipose tissue are involved in the modulation of adrenal steroidogenesis. Aldosterone plasma levels are elevated in obesity and in patients with the metabolic syndrome. Recent research has provided evidence that adipocytes secrete factors that stimulate adrenal mineralocorticoid release and sensitize the adrenal cortex to angiotensin II.

References

  • 1 Seeman TE, Robbins RJ. Aging and hypothalamic-pituitary-adrenal response to challenge in humans.  Endocr Rev. 1994;  15 233-260
  • 2 Zacharowski K, Zacharowski PA, Koch A, Baban A, Tran N, Berkels R, Papewalis C, Schulze-Osthoff K, Knuefermann P, Zahringer U, Schumann RR, Rettori V, MacCann SM, Bornstein SR. Toll-like receptor 4 plays a crucial role in the immune-adrenal response to systemic inflammatory response syndrome.  Proc Natl Acad Sci USA. 2006;  103 6392-6397
  • 3 Bornstein SR, Ziegler CG, Krug AW, Kanczkowski W, Rettori V, MacCann SM, Wirth M, Zacharowski K. The role of toll-like receptors in the immune-adrenal crosstalk.  Ann N Y Acad Sci. 2006;  1088 307-318
  • 4 Bateman A, Singh A, Kral T, Solomon S. The immune-hypothalamic-pituitary-adrenal axis.  Endocr Rev. 1989;  10 92-112
  • 5 Kyrou I, Tsigos C. Stress mechanisms and metabolic complications.  Horm Metab Res. 2007;  39 430-438
  • 6 Bornstein SR, Uhlmann K, Haidan A, Ehrhart-Bornstein M, Scherbaum WA. Evidence for a novel peripheral action of leptin as a metabolic signal to the adrenal gland. Leptin inhibits cortisol release directly.  Diabetes. 1997;  46 1235-1238
  • 7 Johren O, Bruggemann N, Dominiak P. Orexins (hypocretins) and adrenal function.  Horm Metab Res. 2004;  36 370-375
  • 8 Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis.  JAMA. 1992;  267 1244-1252
  • 9 Bornstein SR, Schuppenies A, Wong ML, Licinio J. Approaching the shared biology of obesity and depression: the stress axis as the locus of gene-environment interactions.  Mol Psychiatry. 2006;  11 892-902
  • 10 Korenblum W, Barthel A, Licinio J, Wong ML, Wolf OT, Kirschbaum C, Bornstein SR. Elevated cortisol levels and increased rates of diabetes and mood symptoms in Soviet Union-born Jewish immigrants to Germany.  Mol Psychiatry. 2005;  10 974-975
  • 11 Hanefeld M, Ceriello A, Schwarz PE, Bornstein SR. The challenge of the metabolic syndrome.  Horm Metab Res. 2007;  39 625-626
  • 12 Lamounier-Zepter V, Ehrhart-Bornstein M, Bornstein SR. Metabolic syndrome and the endocrine stress system.  Horm Metab Res. 2006;  38 437-441
  • 13 Salehi A, Ferenczi B, Zumoff B. Obesity and Cortisol Status.  Horm Metab Res. 2005;  37 193-197
  • 14 Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith Jr SC, Spertus JA, Costa F. American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.  Circulation. 2005;  112 2735-2752
  • 15 Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, Williams GR. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults.  Circulation. 2004;  110 1245-1250
  • 16 Hanefeld M, Ceriello A, Schwarz PE, Bornstein SR. The metabolic syndrome – a postprandial disease?.  Horm Metab Res. 2006;  38 435-436
  • 17 Cohn JN, Colucci W. Cardiovascular effects of aldosterone and post-acute myocardial infarction pathophysiology.  Am J Cardiol. 2006;  97 4F-12F
  • 18 Schiffrin EL. Effects of aldosterone on the vasculature.  Hypertension. 2006;  47 312-318
  • 19 Guder G, Bauersachs J, Frantz S, Weismann D, Allolio B, Ertl G, Angermann CE, Stork S. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure.  Circulation. 2007;  115 1754-1761
  • 20 Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.  N Engl J Med. 1999;  341 709-717
  • 21 Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.  N Engl J Med. 2003;  348 1309-1321
  • 22 Kidambi S, Kotchen JM, Grim CE, Raff H, Mao J, Singh RJ, Kotchen TA. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks.  Hypertension. 2007;  49 704-711
  • 23 Bochud M, Nussberger J, Bovet P, Maillard MR, Elston RC, Paccaud F, Shamlaye C, Burnier M. Plasma aldosterone is independently associated with the metabolic syndrome.  Hypertension. 2006;  48 239-245
  • 24 Lamounier-Zepter V, Rotthoff T, Ansurudeen I, Kopprasch S, Scherbaum WA, Ehrhart-Bornstein M, Bornstein SR. Increased aldosterone/renin quotient in obese.  Horm Metab Res. 2006;  38 471-475
  • 25 Bentley-Lewis R, Adler G, Perlstein T, Seely EW, Hopkins PN, Williams GH, Garg R. Body Mass Index predicts aldosterone production in normotensive adults on a high-salt diet.  J Clin Endocrinol Metab. 2007;  92 4472-4475
  • 26 Krug AW, Ehrhart-Bornstein M. Newly discovered endocrine functions of white adipose tissue: possible relevance in obesity-related diseases.  Cell Mol Life Sci. 2005;  62 1359-1362
  • 27 Fischer-Posovszky P, Wabitsch M, Hochberg Z. Endocrinology of adipose tissue – an update.  Horm Metab Res. 2007;  39 314-321
  • 28 Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, Langenbach J, Willenberg HS, Barthel A, Hauner H, MacCann SM, Scherbaum WA, Bornstein SR. Human adipocytes secrete mineralocorticoid-releasing factors.  Proc Natl Acad Sci USA. 2003;  100 14211-14216
  • 29 Ehrhart-Bornstein M, Arakelyan K, Krug AW, Scherbaum WA, Bornstein SR. Fat cells may be the obesity-hypertension link: human adipogenic factors stimulate aldosterone secretion from adrenocortical cells.  Endocr Res. 2004;  30 865-870
  • 30 Krug AW, Vleugels K, Schinner S, Lamounier-Zepter V, Ziegler CG, Bornstein SR, Ehrhart-Bornstein M. Human adipocytes induce an ERK1/2 MAP kinases-mediated upregulation of steroidogenic acute regulatory protein (StAR) and an angiotensin II – sensitization in human adrenocortical cells.  Int J Obes (Lond). 2007;  31 1605-1616
  • 31 Ansurudeen I, Kopprasch S, Ehrhart-Bornstein M, Willenberg HS, Krug AW, Funk RH, Bornstein SR. Vascular-adrenal niche–endothelial cell-mediated sensitization of human adrenocortical cells to angiotensin II.  Horm Metab Res. 2006;  38 476-480
  • 32 Rocchini AP, Key J, Bondie D, Chico R, Moorehead C, Katch V, Martin M. The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents.  N Engl J Med. 1989 Aug 31;  321 580-585
  • 33 Egan BM, Stepniakowski K, Goodfriend TL. Am J Hypertens. 1994;  7 886-893
  • 34 El-Gharbawy AH, Nadig VS, Kotchen JM, Grim CE, Sagar KB, Kaldunski M, Hamet P, Pausova Z, Gaudet D, Gossard F, Kotchen TA. Arterial pressure, left ventricular mass, and aldosterone in essential hypertension.  Hypertension. 2001;  37 845-850
  • 35 Nagase M, Yoshida S, Shibata S, Nagase T, Gotoda T, Ando K, Fujita T. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors.  J Am Soc Nephrol. 2006;  17 3438-3446
  • 36 Rahmouni K, Correia ML, Haynes WG, Mark AL. Obesity-associated hypertension: new insights into mechanisms.  Hypertension. 2005;  45 9-14

Correspondence

Dr. med. A. W. Krug

Medical Clinic III

Technical University of Dresden

Department of Endocrinology

Diabetology, and Metabolism

Fetscherstraße 74

01307 Dresden

Germany

Phone: +49/3514/58 59 40

Fax: +49/3514/58 63 98

Email: Alexander.Krug@uniklinikum-dresden.de

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