Endocrine (2013) 43:444–446 DOI 10.1007/s12020-012-9816-7
RESEARCH LETTER
Changes in adipokines but not in body composition after one week of prednisone intake in physically fit women Laetitia Jollin • Nathalie Rieth • Re´my Thomasson Virgile Amiot • Franc¸oise Lasne • Katia Collomp
•
Received: 12 July 2012 / Accepted: 5 October 2012 / Published online: 13 October 2012 ! Springer Science+Business Media New York 2012
Introduction
Materials and methods
Long-term glucocorticoid (GC) treatment has many known side effects, but the few studies that focused on short-term GC treatment have shown contradictory results. Regardless of whether short-term GC has or does not have negative effects on skeletal health, as is suspected [1], its administration induces weight gain [2, 3] or does not [4–6], in association with increased food intake [2] or not [5], in healthy young men [2–5] and postmenopausal women [6]. Glucocorticoids also alter the adipokine secretion (i.e., leptin and adiponectin) involved in the regulation of food intake. Although almost all studies have reported an increase in leptin with both the long-term and short-term GC treatments, the effects on adiponectin have been more controversial [5–9]. As clinical applications for GCs are expanding worldwide because of their anti-inflammatory and immunosuppressive effects, it is important to determine whether 1 week of GC treatment has major adverse effects on body composition or adipokines in healthy, young, and physically fit women.
Subjects
L. Jollin ! N. Rieth (&) ! R. Thomasson ! K. Collomp Laboratoire CIAMS, Universite´ Paris Sud – Universite´ Orle´ans, 2, Alle´e du Chaˆteau, BP 6237 45062, Orle´ans Cedex 2, France e-mail:
[email protected] V. Amiot Service de Me´decine du Sport CHR, Orle´ans Cedex 2, France F. Lasne ! K. Collomp De´partement des Analyses, Agence Franc¸aise de Lutte contre le Dopage, Chatenay-Malabry, France
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The protocol was approved by the local ethics committee. Seventeen healthy young Caucasian women (19.9 ± 1.1 years) with normal body mass index (22.4 ± 2.3), taking low-dose oral contraceptive pills, and having regular physical activity (between 4 and 6 h per week) were required to maintain similar exercise patterns and normal food intake throughout the duration of the experiment, which was always performed during the second part of the menstrual cycle.
Treatment The study was double-blind and randomized, with two 1-week treatment periods separated by a 4-week washout period. Prednisone (50 mg/day; Pred: trade name Cortancyl 5 mg, tablet, Sanofi-Aventis Laboratory, Paris) and placebo (Pla: gelatin) were administered over 7 days in the same capsules between 7 and 8 am. Fifty milligrams of prednisone is a relatively large therapeutic dose, equivalent to 200 mg/day of hydrocortisone, 40 mg/day of methylprednisolone, and 8 mg/day of dexamethasone.
Protocol and analysis Food records were collected from the subjects on the last 3 days of each treatment period for total energy intake (TEI) and macronutrient determination. Diet records were analyzed using Bilnut" software. Subjects’ body weight and body composition were assessed—the latter by skinfold thickness measurement—
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by the same investigator before and at the end of each treatment Blood samples were taken between 10 and 11 am the day before and on the last day of each treatment, one hour after ingesting a small meal, which was identical for each trial. Samples were promptly centrifuged and stored at -72 #C until leptin and adiponectin determination by ELISA tests (Bioadvance, France). All assays were made in duplicate. Coefficients of variation (inter- and intra-assay) for all parameters were always \ 10 %.
leptin (ng/ml)
15
*
13 11 9 7 5
bef Pla
bef Pred
aft Pred
adiponectin (µg/ml)
15
Statistical analysis
aft Pla
13
Data are presented as mean values ± standard error of the mean (SE). Differences were analyzed with a two-way analysis of variance with repeated measures, and a post hoc Newman– Keuls test was used to locate the differences if necessary. The limit of significance was P \ 0.05.
Results Prednisone did not modify body weight or fat mass, and macronutrient intake did not significantly change during the study (Table 1). Leptin and adiponectin levels were significantly higher at the end-treatment of Pred vs. baseline (P \ 0.05, Fig. 1).
Discussion No significant changes in body weight, body composition, or energy intake were found after short-term prednisone intake in the studied healthy young women. These results partly contradicted other study findings [2, 3, 6]. Tataranni et al. [2] found a significant increase in body weight after 4 days of 40 mg methylprednisolone treatment, associated with significantly increased food intake, in healthy young
*
11 9 7 5
bef Pla
aft Pla
bef Pred
aft Pred
Fig. 1 Leptin and adiponectin concentrations before (bef) and after (aft) placebo (Pla) and prednisone (Pred) treatment. Leptin and adiponectin levels were significantly increased with Pred at endtreatment vs. pre-treatment (*P \ 0.05) but not with Pla (leptin: P = 0.71; adiponectin: P = 0.33)
male volunteers. Udden et al. [6] found that 7 days of 25 mg prednisolone treatment increased food intake with no change in body weight in postmenopausal women. Last, Patel et al. [3] demonstrated significantly increased body mass index in healthy young men after only 5 days of 6 mg dexamethasone, but their food intake was not investigated. The results of this study nevertheless agree with those of other studies, which reported no alteration in body weight in sedentary healthy men after 2 days of 6 mg dexamethasone [4] or in healthy recreationally trained men after 7 days of 60 mg prednisolone administration [5]. As did Rieth et al. [5], we suggest that our subjects’ daily exercise may have counteracted or delayed the increase in dietary
Table 1 Effect of placebo (Pla) and prednisone (Pred) treatment on body weight, fat mass, and food intake Pla Before
Pred After
Before
After
P
Treatment
P
Time
Body weight (kg)
61.1 ± 1.4
61.7 ± 1.5
60.8 ± 1.4
61.8 ± 1.2
P = 0.93
P = 0.57
Fat mass (%)
24.9 ± 1.1
25.5 ± 1.1
24.4 ± 1.0
25.2 ± 1.0
P = 0.74
P = 0.52
6,525.7 ± 370.1
6,677.9 ± 393.6
6,621.2 ± 456.3
7,350.1 ± 432.1
P = 0.36
P = 0.29
Carbohydrate (% TEI)
51.9 ± 1.5
50.4 ± 1.4
50.3 ± 1.4
49.6 ± 1.1
P = 0.38
P = 0.41
Fat (% TEI) Proteins (% TEI)
32.5 ± 1.2 15.6 ± 0.8
33.5 ± 1.3 16.2 ± 1.1
33.2 ± 1.3 16.5 ± 1
33.7 ± 1.4 16.7 ± 1.1
P = 0.72 P = 0.49
P = 0.57 P = 0.71
TEI (kJ)
No significant difference between treatments (Pred vs. Pla) or times (after vs. before treatment) was observed
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intake and/or fat mass gain potentially induced by 1 week of GC per os treatment. Glucocorticoids are thought to be potent stimulators of ob gene expression and thus of circulating leptin levels, which signal satiety through hypothalamic pathways [9]. In accordance with the literature [5–9], we demonstrated a significant increase in leptin levels after prednisone treatment. Given the maintained body composition, serum leptin may be regulated by GCs independently of changes in body fat mass. In parallel, the lack of increased dietary intake under prednisone treatment may result from the satiety effect of leptin counteracting the direct and/or indirect [2] appetite-stimulating effects of GCs [9]. This also confirms that appetite regulation is multifactorial, with other neurotransmitter pathways presumably involved [9]. Previous data on adiponectin appear conflicting. Indeed, Patel et al. [3] found no change in adiponectin after 5 days of 6 mg dexamethasone despite dexamethasone-related increases in body weight, whereas Jang et al. [8] demonstrated that 4 days of 4 mg dexamethasone induced a small rise in plasma adiponectin levels in nondiabetic subjects. Last, Rieth et al. [5] found a significant increase in adiponectin concentrations in healthy recreationally trained men after 7 days of 60 mg prednisone administration. In line with this last study, we found significantly higher adiponectin levels after prednisone vs. placebo treatment, but without significant correlation between leptin and adiponectin. It therefore appears that short-term prednisone intake affects adiponectin release favorably, with a possible prednisone– adiponectin interaction against detrimental GC effects, but further investigation is needed to confirm this hypothesis. In conclusion, this study ruled out major adverse effects of one week of GC ingestion on fat mass in healthy, physically fit women, despite a leptin increase. Further studies are needed to assess other potential side effects of short-term GC administration in this population, such as inhibition of GH secretion, which may directly influence the final metabolic effects [10].
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Endocrine (2013) 43:444–446 Acknowledgments This project was carried out with the support of WADA (World Anti-doping Agency). The authors wish to express their gratitude to the subjects for their dedicated performance. In addition, we thank the CHR of Orle´ans, Dr. Anne-Marie Lecoq, Cathy Carmeni, Nathalie Cre´pin, Nicole Chevrier, Sylvie Desforges, Sandra Ferary, Patrick Guenon, Johan Le-Drogoff, and Patrick Marie for their expert assistance.
References 1. G. Mazziotti, A. Angeli, J.P. Bilezikian, E. Canalis, A. Giustina, Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol. Metab. 17, 144–149 (2006) 2. P.A. Tataranni, D.E. Larson, S. Snitker, J.B. Young, J.P. Flatt, E. Ravussin, Effects of glucocorticoids on energy metabolism and food intake in humans. Am. J. Physiol. 271, E317–E325 (1996) 3. J. Patel, D. Cummings, J. Girod, A. Mascarenhas, E. Hughes, M. Gupta, G.Y. Lip, S. Reddy, D.J. Brotman, Role of metabolically active hormones in the insulin resistance associated with short-term glucocorticoid treatment. J. Negat. Results Biomed. 5, 14 (2006) 4. J. Beard, J. Halter, J. Best, M. Pfeifer, D. Porte, Dexamethasoneinduced insulin resistance enhances B cell responsiveness to glucose level in normal men. Am. J. Physiol. 247, E592–E596 (1984) 5. N. Rieth, L. Jollin, B. Le Panse, A.M. Lecoq, A. Arlettaz, J. De Ceaurriz, K. Collomp, Effects of short-term corticoid ingestion on food intake and adipokines in healthy recreationally trained men. Eur. J. Appl. Physiol. 105, 309–313 (2009) 6. J. Udden, P. Bjo¨rntorp, P. Arner, B. Barkeling, L. Meurling, S. Ro¨ssner, Effects of glucocorticoids on leptin levels and eating behaviour in women. J. Intern. Med. 253, 225–231 (2003) 7. H. Larsson, B. Ahren, Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women. J. Clin. Endocrinol. Metab. 81, 4428–4432 (1996) 8. C. Jang, W. Inder, V. Obeyesekere, F. Alford, Adiponectin, skeletal muscle adiponectin receptor expression and insulin resistance following dexamethasone. Clin. Endocrinol. 69, 745–750 (2008) 9. J.P. Miell, P. Englaro, W.F. Blum, Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects. Horm. Metab. Res. 28, 704–707 (1996) 10. A. Giustina, M. Doga, C. Bodini, A. Girelli, F. Legati, S. Bossoni, G. Romanelli, Acute effects of cortisone acetate on growth hormone response to growth hormone-releasing hormone in normal adult subjects. Acta Endocrinol. 122, 206–210 (1990)
