Aldosterone Inhibits Uncoupling Protein-1, Induces Insulin Resistance, and Stimulates Proinflammatory Adipokines in Adipocytes

Abstract

Aldosterone is a mineralocorticoid hormone that regulates blood pressure and salt/water balance. Increased aldosterone levels are found in states of disturbed energy balance such as the metabolic syndrome. Adipose tissue has been recognized to play a pivotal role in the regulation of energy homeostasis. We investigated direct aldosterone effects on brown adipocyte function. Aldosterone dose-dependently inhibited expression of uncoupling protein-1 (UCP-1) by 30 % (p < 0.01). Furthermore, aldosterone dose-dependently impaired insulin-induced glucose uptake by about 25 % (p < 0.01). On a transcriptional level, mRNA of the proinflammatory adipokines leptin and monocyte chemoattractant protein-1 (MCP-1) was increased by 5,000 % and 40 %, respectively, by aldosterone exposure (p < 0.05). This study demonstrates that aldosterone directly impacts on major adipose functions including stimulation of proinflammatory adipokines.

Key words

Adipose tissue - Metabolic syndrome - Monocyte-chemoattractant protein-1

References

• 1 Isomaa B. A major health hazard: the metabolic syndrome.  Life Sci. 2003;  73 2395-2411
• 2 Engeli S, Bohnke J, Gorzelniak K, Janke J, Schling P, Bader M, Luft F C, Sharma A M. Weight loss and the renin-angiotensin-aldosterone system.  Hypertension. 2005;  45 356-362
• 3 Lamounier-Zepter V, Bornstein S R, Ehrhart-Bornstein M. Mechanisms of obesity-related hypertension.  Horm Metab Res. 2004;  36 376-380
• 4 Sharma A M, Engeli S, Pischon T. New developments in mechanisms of obesity-induced hypertension: role of adipose tissue.  Curr Hypertens Rep. 2001;  3 152-156
• 5 Rajala M W, Scherer P E. Minireview: The adipocyte - at the crossroads of energy homeostasis, inflammation, and atherosclerosis.  Endocrinology. 2003;  144 3765-3773
• 6 Minokoshi Y, Kahn C R, Kahn B B. Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis.  J Biol Chem. 2003;  278 33 609-33 612
• 7 Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance.  Physiol Rev. 2004;  84 277-359
• 8 Krief S, Lonnqvist F, Raimbault S, Baude B, van Spronsen A, Arner P, Strosberg A D, Ricquier D, Emorine L J. Tissue distribution of beta 3-adrenergic receptor mRNA in man.  J Clin Invest. 1993;  91 344-349
• 9 Yang X, Enerback S, Smith U. Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance.  Obes Res. 2003;  11 1182-1191
• 10 Engeli S, Schling P, Gorzelniak K, Boschmann M, Janke J, Ailhaud G, Teboul M, Massiera F, Sharma A M. The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?.  Int J Biochem Cell Biol. 2003;  35 807-825
• 11 Engeli S, Sharma A M. The renin-angiotensin system and natriuretic peptides in obesity-associated hypertension.  J Mol Med. 2001;  79 21-29
• 12 Goossens G H, Blaak E E, van Baak M A. Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders.  Obes Rev. 2003;  4 43-55
• 13 Kraus D, Fasshauer M, Klein J. Neuropeptide and peripheral hormone crosstalk with adipocyte function.  Adipocytes. 2005;  in press
• 14 Klein J, Fasshauer M, Ito M, Lowell B B, Benito M, Kahn C R. beta(3)-adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes.  J Biol Chem. 1999;  274 34 795-34 802
• 15 Klein J, Fasshauer M, Klein H H, Benito M, Kahn C R. Novel adipocyte lines from brown fat: a model system for the study of differentiation, energy metabolism, and insulin action.  Bioessays. 2002;  24 382-388
• 16 Pfaffl M W, Horgan G W, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR.  Nucleic Acids Res. 2002;  30 e36
• 17 Fasshauer M, Klein J, Kralisch S, Klier M, Lossner U, Bluher M, Paschke R. Monocyte chemoattractant protein 1 expression is stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes.  Biochem Biophys Res Commun. 2004;  317 598-604
• 18 Friedman J M. The function of leptin in nutrition, weight, and physiology.  Nutr Rev. 2002;  60 S1-S14; discussion S68 - S84, 85 - 87
• 19 Christiansen T, Richelsen B, Bruun J M. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects.  Int J Obes Relat Metab Disord. 2005;  29 146-150
• 20 Sartipy P, Loskutoff D J. Monocyte chemoattractant protein 1 in obesity and insulin resistance.  Proc Natl Acad Sci U S A. 2003;  100 7265-7270
• 21 Viengchareun S, Penfornis P, Zennaro M C, Lombes M. Mineralocorticoid and glucocorticoid receptors inhibit UCP expression and function in brown adipocytes.  Am J Physiol Endocrinol Metab. 2001;  280 E640-E649
• 22 Penfornis P, Viengchareun S, Le Menuet D, Cluzeaud F, Zennaro M C, Lombes M. The mineralocorticoid receptor mediates aldosterone-induced differentiation of T37i cells into brown adipocytes.  Am J Physiol Endocrinol Metab. 2000;  279 E386-E394
• 23 Kraus D, Fasshauer M, Ott V, Meier B, Jost M, Klein H H, Klein J. Leptin secretion and negative autocrine crosstalk with insulin in brown adipocytes.  J Endocrinol. 2002;  175 185-191
• 24 Buyse M, Viengchareun S, Bado A, Lombes M. Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes.  FASEB J. 2001;  15 1357-1366
• 25 Kershaw E E, Flier J S. Adipose tissue as an endocrine organ.  J Clin Endocrinol Metab. 2004;  89 2548-2556
• 26 Torpy D J, Bornstein S R, Taylor W, Tauchnitz R, Gordon R D. Leptin levels are suppressed in primary aldosteronism.  Horm Metab Res. 1999;  31 533-536
• 27 Haluzik M, Sindelka G, Widimsky J Jr, Prazny M, Zelinka T, Skrha J. Serum leptin levels in patients with primary hyperaldosteronism before and after treatment: relationships to insulin sensitivity.  J Hum Hypertens. 2002;  16 41-45
• 28 Wisse B E. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity.  J Am Soc Nephrol. 2004;  15 2792-2800