Journal of Clinical Endocrinology & Metabolism, Vol 81, 4428-4432, Copyright © 1996 by Endocrine Society

ARTICLES

Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women

H Larsson and B Ahren
Department of Medicine, Lund University, Malmo, Sweden. Hillevi.Larsson@medforsk.mas.lu.se

Leptin has been demonstrated to correlate with body fat content in humans, but the regulation of leptin levels is poorly understood. Therefore, we studied the relation between fasting insulin, plasma leptin, and insulin sensitivity, as assessed by the hyperinsulinemic euglycemic clamp, before and after short term corticosteroid treatment, which is known to induce insulin resistance (3.0 mg dexamethasone, twice daily, for 48 h; total dose, 15 mg) in nine healthy women (mean +/- SE age, 58.6 +/- 0.1 yr; body mass index, 25.9 +/- 1.7 kg/m2). Dexamethasone increased fasting leptin levels by 114 +/- 14% (18.4 +/- 3.3 vs. 39.4 +/- 7.3 ng/ml; P = 0.001) and increased fasting insulin by 51 +/- 12% (P = 0.004). Concomitantly, insulin sensitivity was reduced to 45 +/- 5% (P = 0.001). The increase in leptin correlated with the reduction of insulin sensitivity (r = 0.68; P = 0.044), but this correlation was no longer significant after correction for body mass index. The correlation between the change in plasma leptin and body mass index (r = 0.79; P = 0.012), however, was independent of the change in both fasting insulin and insulin sensitivity. We conclude that short term corticosteroid treatment induces a doubling of fasting leptin in healthy humans. The dexamethasone-induced increase in leptin is dependent of body mass index, but not of insulin levels or insulin sensitivity, which suggests that the influence of dexamethasone on plasma leptin is not mediated by its influences on fasting insulin or insulin sensitivity.

This article has been cited by other articles:

				J. W. Tomlinson, J. Finney, B. A. Hughes, S. V. Hughes, and P. M. Stewart Reduced Glucocorticoid Production Rate, Decreased 5{alpha}-Reductase Activity, and Adipose Tissue Insulin Sensitization After Weight Loss Diabetes, June 1, 2008; 57(6): 1536 - 1543. [Abstract] [Full Text] [PDF]

				L. L. Gathercole, I. J. Bujalska, P. M. Stewart, and J. W. Tomlinson Glucocorticoid Modulation of Insulin Signaling in Human Subcutaneous Adipose Tissue J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4332 - 4339. [Abstract] [Full Text] [PDF]

				H. Muller, N. Schweitzer, O. Johren, P. Dominiak, and W. Raasch Angiotensin II stimulates the reactivity of the pituitary-adrenal axis in leptin-resistant Zucker rats, thereby influencing the glucose utilization Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E802 - E810. [Abstract] [Full Text] [PDF]

				S. Dagogo-Jack, G. Tykodi, and I. Umamaheswaran Inhibition of Cortisol Biosynthesis Decreases Circulating Leptin Levels in Obese Humans J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5333 - 5335. [Abstract] [Full Text] [PDF]

				J. A. Cartmill, D. L. Thompson Jr., W. A. Storer, J. C. Crowley, N. K. Huff, and C. A. Waller Effect of dexamethasone, feeding time, and insulin infusion on leptin concentrations in stallions J Anim Sci, August 1, 2005; 83(8): 1875 - 1881. [Abstract] [Full Text] [PDF]

				J. Calissendorff, O. Danielsson, K. Brismar, and S. Rojdmark Inhibitory effect of alcohol on ghrelin secretion in normal man Eur. J. Endocrinol., May 1, 2005; 152(5): 743 - 747. [Abstract] [Full Text] [PDF]

				J. CALISSENDORFF, K. BRISMAR, and S. ROJDMARK IS DECREASED LEPTIN SECRETION AFTER ALCOHOL INGESTION CATECHOLAMINE-MEDIATED? Alcohol Alcohol., July 1, 2004; 39(4): 281 - 286. [Abstract] [Full Text] [PDF]

				I.A. Harsch, P.C. Konturek, C. Koebnick, P.P. Kuehnlein, F.S. Fuchs, S. Pour Schahin, G.H. Wiest, E.G. Hahn, T. Lohmann, and J.H. Ficker Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment Eur. Respir. J., August 1, 2003; 22(2): 251 - 257. [Abstract] [Full Text] [PDF]

				A. E. Kitabchi and G. E. Umpierrez Changes in Serum Leptin in Lean and Obese Subjects with Acute Hyperglycemic Crises J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2593 - 2596. [Abstract] [Full Text] [PDF]

				L. R. Gentry, D. L. Thompson Jr., G. T. Gentry Jr., K. A. Davis, and R. A. Godke High versus low body condition in mares: Interactions with responses to somatotropin, GnRH analog, and dexamethasone J Anim Sci, December 1, 2002; 80(12): 3277 - 3285. [Abstract] [Full Text] [PDF]

				H. S. Randeva, R. D. Murray, K. C. Lewandowski, C. J. O'Callaghan, R. Horn, P. O'Hare, G. Brabant, E. W. Hillhouse, and S. M. Shalet Differential Effects of GH Replacement on the Components of the Leptin System in GH-Deficient Individuals J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 798 - 804. [Abstract] [Full Text] [PDF]

				J. J. Reilly, M. Brougham, C. Montgomery, F. Richardson, A. Kelly, and B. E. S. Gibson Effect of Glucocorticoid Therapy on Energy Intake in Children Treated for Acute Lymphoblastic Leukemia J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3742 - 3745. [Abstract] [Full Text] [PDF]

				M. BUYSE, S. VIENGCHAREUN, A. BADO, and M. LOMBES Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes FASEB J, June 1, 2001; 15(8): 1357 - 1366. [Abstract] [Full Text] [PDF]

				S. K. Fried, M. R. Ricci, C. D. Russell, and B. Laferrere Regulation of Leptin Production in Humans J. Nutr., December 1, 2000; 130 (12): 3127S - 3131S. [Abstract] [Full Text] [PDF]

				I.E. Messinis, I. Kariotis, S. Milingos, G. Kollios, and K. Seferiadis Treatment of normal women with oestradiol plus progesterone prevents the decrease of leptin concentrations induced by ovariectomy Hum. Reprod., November 1, 2000; 15(11): 2383 - 2387. [Abstract] [Full Text] [PDF]

				G. GARIBOTTO, A. BARRECA, A. SOFIA, R. RUSSO, F. FIORINI, G. CAPPELLI, F. CAVATORTA, A. CESARONE, R. FRANCESCHINI, P. SACCO, et al. Effects of Growth Hormone on Leptin Metabolism and Energy Expenditure in Hemodialysis Patients with Protein-Calorie Malnutrition J. Am. Soc. Nephrol., November 1, 2000; 11(11): 2106 - 2113. [Abstract] [Full Text]

				P C Ng, C W K Lam, C H Lee, G W K Wong, T F Fok, E Wong, K C Ma, and I H S Chan Leptin and metabolic hormones in infants of diabetic mothers Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2000; 83(3): 193F - 197. [Abstract] [Full Text]

				P C Ng, C W K Lam, C H Lee, G W K Wong, T F Fok, I H S Chan, K C Ma, and E Wong Leptin and metabolic hormones in preterm newborns Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2000; 83(3): 198F - 202. [Abstract] [Full Text]

				L. B. Williams, R. L. Fawcett, A. S. Waechter, P. Zhang, B. E. Kogon, R. Jones, M. Inman, J. Huse, and R. V. Considine Leptin Production in Adipocytes from Morbidly Obese Subjects: Stimulation by Dexamethasone, Inhibition with Troglitazone, and Influence of Gender J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2678 - 2684. [Abstract] [Full Text]

				C. A. Mastronardi, A. Walczewska, W. H. Yu, S. Karanth, A. F. Parlow, and S. M. McCann The Possible Role of Prolactin in the Circadian Rhythm of Leptin Secretion in Male Rats Experimental Biology and Medicine, July 1, 2000; 224(3): 152 - 158. [Abstract] [Full Text]

				M. S. Buchowski, L. A. Simmons, K. Y. Chen, P. J. Flakoll, B. G. Mellen, and E. A. Turner Plasma Leptin Association with Body Composition and Energy Expenditure in Sickle Cell Disease J. Am. Coll. Nutr., April 1, 2000; 19(2): 228 - 236. [Abstract] [Full Text] [PDF]

				M. Landt Leptin Binding and Binding Capacity in Serum Clin. Chem., March 1, 2000; 46(3): 379 - 384. [Abstract] [Full Text] [PDF]

				M. Weise, V. Abad, R. V. Considine, L. Nieman, and K. I. Rother Leptin Secretion in Cushing's Syndrome: Preservation of Diurnal Rhythm and Absent Response to Corticotropin-Releasing Hormone J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2075 - 2079. [Abstract] [Full Text]

				C. S. Mantzoros The Role of Leptin in Human Obesity and Disease: A Review of Current Evidence Ann Intern Med, April 20, 1999; 130(8): 671 - 680. [Abstract] [Full Text] [PDF]

				F-X. Pi-Sunyer and B. Laferrère Metabolic Abnormalities and the Role of Leptin in Human Obesity J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 3 - 7. [Full Text]

				J. W. Newcomer, G. Selke, A. K. Melson, J. Gross, G. P. Vogler, and S. Dagogo-Jack Dose-Dependent Cortisol-Induced Increases in Plasma Leptin Concentration in Healthy Humans Arch Gen Psychiatry, November 1, 1998; 55(11): 995 - 1000. [Abstract] [Full Text] [PDF]

				M. Miyakawa, T. Tsushima, H. Murakami, O. Isozaki, H. Demura, and T. Tanaka Effect of Growth Hormone (GH) on Serum Concentrations of Leptin: Study in Patients with Acromegaly and GH Deficiency J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3476 - 3479. [Abstract] [Full Text]

				C. D. Russell, R. N. Petersen, S. P. Rao, M. R. Ricci, A. Prasad, Y. Zhang, R. E. Brolin, and S. K. Fried Leptin expression in adipose tissue from obese humans: depot-specific regulation by insulin and dexamethasone Am J Physiol Endocrinol Metab, September 1, 1998; 275(3): E507 - E515. [Abstract] [Full Text] [PDF]

				D. Torpy, S. Bornstein, G Cizza, and G. Chrousos The Effects of Glucocorticoids on Leptin Levels in Humans May Be Restricted to Acute Pharmacologic Dosinga J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1821 - 1822. [Full Text]

				C. M. Halleux, I. Servais, B. A. Reul, R. Detry, and S. M. Brichard Multihormonal Control of ob Gene Expression and Leptin Secretion from Cultured Human Visceral Adipose Tissue: Increased Responsiveness to Glucocorticoids in Obesity J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 902 - 910. [Abstract] [Full Text]

				A. Widjaja, T. H. Schürmeyer, A. Von Zur Mühlen, and G. Brabant Determinants of Serum Leptin Levels in Cushing's Syndrome J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 600 - 603. [Abstract] [Full Text]

				W. T. Donahoo, D. R. Jensen, T. J. Yost, and R. H. Eckel Isoproterenol and Somatostatin Decrease Plasma Leptin in Humans: A Novel Mechanism Regulating Leptin Secretion J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4139 - 4143. [Abstract] [Full Text] [PDF]

				J. W. Kolaczynski, B. J. Goldstein, and R. V. Considine Dexamethasone, OB Gene, and Leptin in Humans; Effect of Exogenous Hyperinsulinemia J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3895 - 3897. [Abstract] [Full Text] [PDF]

				S. Dagogo-Jack, G. Selke, A. K. Melson, and J. W. Newcomer Robust Leptin Secretory Responses to Dexamethasone in Obese Subjects J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3230 - 3233. [Abstract] [Full Text] [PDF]

				J. E. Janik, B. D. Curti, R. V. Considine, H. C. Rager, G. C. Powers, W. G. Alvord, J. W. Smith II, B. L. Gause, and W. C. Kopp Interleukin 1{alpha} Increases Serum Leptin Concentrations in Humans J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 3084 - 3086. [Abstract] [Full Text] [PDF]

				G. Cizza, A. J. Lotsikas, J. Licinio, P. W. Gold, and G. P. Chrousos Plasma Leptin Levels Do not Change in Patients with Cushing's Disease Shortly after Correction of Hypercortisolism J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2747 - 2750. [Abstract] [Full Text] [PDF]