Subscribe to RSS
DOI: 10.1055/s-0043-100383
Peripheral and Central Glucocorticoid Signaling Contributes to Positive Energy Balance in Rats
Publication History
received 29 August 2016
accepted 22 December 2016
Publication Date:
21 April 2017 (online)
![](https://www.thieme-connect.de/media/hmr/201706/lookinside/thumbnails/2016-12-0388_10-1055-s-0043-100383-1.jpg)
Abstract
The obesity epidemic has been the target of several studies to understand its etiology. The pathophysiological processes that take to obesity generally relate to the rupture of energy balance. This imbalance can result from environmental and/or endogenous events. Among the endogenous events, the hypothalamic-pituitary-adrenal axis, which promotes stress response via glucocorticoid activity, is considered a modulator of energy balance. However, it remains controversial whether the increase in plasma levels of glucocorticoids results in a positive or negative energy balance. Furthermore, there are no studies comparing different routes of administration of glucocorticoids in this context. Here, we investigated the effects of intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of a specific agonist for glucocorticoid receptors on food intake and energy expenditure in rats. Sixty-day old rats were treated with i.p. or i.c.v. dexamethasone. Food intake and satiety were evaluated, as well as locomotor activity in order to determine energy expenditure. Both i.p. and i.c.v. dexamethasone increased food intake and decreased energy expenditure. Moreover, i.c.v. dexamethasone delayed the onset of satiety. Together, these results confirm that central glucocorticoid signaling promotes a positive energy balance and supports the role of the glucocorticoid system as the underlying cause of psychological stress-induced obesity.
Supporting Information
- Supporting Information for this article is available online at
http://www.thieme-connect.de/products
- Supporting Information
-
References
- 1 James WP. The epidemiology of obesity. Ciba Found Symp 1996; 201: 1-11
- 2 Lu D, Willard D, Patel IR, Kadwell S, Overton L, Kost T, Luther M, Chen W, Woychik RP, Wilkison WO, Coner RD. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 1994; 371: 799-802
- 3 Cota D, Proulx K, Seeley RJ. The role of CNS fuel sensing in energy and glucose regulation. Gastroenterology 2007; 132: 2158-2168
- 4 Cone RD, Cowley MA, Butler AA, Fan W, Marks DL, Low MJ. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int J Obes Relat Metab Disord 2001; 5: S637
- 5 Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, Kuhal MJ, Saper CB, Elmquist JK. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 1998; 21: 1375-1385
- 6 Broberger C, Johansen J, Johansson C, Schalling M, Hokfelt T. The neuropeptide Y/agouti generelated protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl AcadSci U S A 1998; 95: 15043-15048
- 7 Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543-546
- 8 Gillies GE, Linton EA, Lowry PJ. Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin. Nature 1982; 299: 355-357
- 9 Chalmers DT, Lovenberg TW, De Souza EB. Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: Comparison with CRF1 receptor mRNA expression. J Neurosci 1995; 15: 6340-6350
- 10 Dallman MF, Akana SF, Cascio CS, Darlington DN, Jacobson L, Levin N. Regulation of ACTH secretion: Variations on a theme of B. Recent ProgHorm Res 1987; 43: 113-173
- 11 Reul JM, de Kloet ER. Two receptor systems for corticosterone in rat brain: Microdistribution and differential occupation. Endocrinology 1985; 117: 2505-2511
- 12 Nishi M, Kawata M. Brain corticosteroid receptor dynamics and traf- ficking: Implications from live cell imaging. Neuroscientist 2006; 12: 119-133
- 13 Sominsky L, Spencer SJ. Eating behavior and stress: a pathway to obesity. Front Psychol 2014; 5: 434
- 14 Santana P, Akana SF, Hanson ES, Strack AM, Sebastian RJ, Dallman MF. Aldosterone and dexamethasone both stimulate energy acquisition whereas only the glucocoticoid alters energy storage. Endocrinology 1995; 136: 2214-2222
- 15 Devenport L, Knehans A, Thomas T, Sundstrom A. Macronutrient intake and utilization by rats: interactions with type I adrenocorticoid receptor stimulation. Am J Physiol 1991; 260 1 Pt 2 R73-R81
- 16 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: 365-367
- 17 Shibli-Rahhal M, Van Beek JA. Shlechte, Cushing’s syndrme. Clin Dermatol 2006; 24: 260-265
- 18 Liu XY, Shi JH, Du WH, Fan YP, Hu XL, Zhang CC, Xu HB, Miao YJ, Zhou HY, Xiang P, Chen FL. Glucocorticoids decrease body weight and food intake and inhibit appetite regulatory peptide. Exp Ther Med 2011; 2: 977-984
- 19 Jahng JW, Kim NY, Ryu V, Yoo SB, Kim BT, Kang DW, Lee JH. Dexamethasone reduces food intake, weight gain and the hypothalamic 5-HT concentration and increases plasma leptin in rats. Eur J Pharmacol 2008; 581: 64-70
- 20 Aja S, Bi S, Knipp SB, McFadden JM, Ronnett GV, Kuhajda FP, Moran TH. Intracerebroventricular C75 decreases meal frequency and reduces AgRP gene expression in rats. Am J Physiol 2006; 291: 148-154
- 21 Briski KP, DiPasquale BM, Gillen E. Induction of immediate-early gene expression in preoptic and hypothalamic neurons by the glucocorticoid receptor agonist, dexamethasone. Brain Res 1997; 768: 185-196
- 22 Casarotto PC, Andreatini R. Repeated paroxetine treatment reverses anhedonia induced in rats by chronic mild stress or dexamethasone. Eur Neuropsychopharmacol 2007; 17: 735-742
- 23 Westerterp KR. Physical activity and physical activity induced energy expediture in humans: measurement, determinants and effects. Front Physiol 2013; 26: 4-90
- 24 Aragão R, da S, Rodrigues MA, de Barros KM, Silva SR, Toscano AE, de Souza RE, Manhães-de Castro R. Automatic system for analysis of locomotor activity in rodents a reproducibility study. J Neurosci Meth 2011; 195: 216-221
- 25 Silva KO, Pereira Sda C, Portovedo M, Milanski M, Galindo LC, Guzmán-Quevedo O, Manhães-de-Castro R, Toscano AE. Effects of maternal low-protein diet on parameters of locomotor activity in a rat model of cerebral palsy. Int J Dev Neurosci 2016; 52: 38-45
- 26 Golozoubova V, Strauss F, Malmlof K. Locomotion is tha major determinant of sibutramine-induced increased in energy expenditure. Pharmacol Biochem Behav 2006; 83: 517-527
- 27 Tempel DL, Leibowitz SF. Adrenal steroid receptors: interactions with brain neuropeptide systems in relation to nutrient intake and metabolism. J Neuroendocrinol 1994; 479-501
- 28 Sujino M, Furukawa K, Koinuma S, Fujioka A, Nagano M, Iigo M, Shigeyoshi Y. Differential entrainment of peripheral clocks in the rat by glucocorticoid and feeding. Endocrinology 2012; 153: 2277-2286
- 29 Sainbury A, Cusin I, Rohner-Jeanrenaud F, Jeanrenaud B. Adrenalectomy prevents the obesity syndrome produced by chronic central neuropeptide Y infusion in normal rats. Diebetes 1997; 46: 209-214
- 30 Lee B, Kim SG, Kim J, Choi KY, Lee S, Lee SK, Lee JW. Brain-specific homeobox factor as a target selector for glucocorticoid receptor in energy balance. Mol Cell Biol 2013; 33: 2650-2658
- 31 Sandri M. Autophagy in skeletal muscle. FEBS Lett 2010; 584: 1411-1416
- 32 Reul JM, de Kloet ER. Two receptor systems for corticosterone in rat brain: Microdistribution and differential occupation. Endocrinology 1985; 117: 2505-2511
- 33 Vegiopoulos A, Herzig S. Glucocorticoids, metabolism and metabolic diseases. Mol Cell Endocrinol. 2007; 275: 43-61
- 34 Weinstein SP, Wilson CM, Pritsker A, Cushman SW. Dexamethasone inhibits insulin-stimulated recruitment of GLUT4 to the cell surface in rat skeletal muscle. Metabolism 1998; 47: 3-6
- 35 Waddell DS, Baehr LM, van den Brandt J, Johnsen SA, Reichardt HM, Furlow JD, Bodine SC. The glucocorticoid receptor and FOXO1 synergistically activate the skeletal muscle atrophy-associated MuRF1 gene. Am J Physiol Endocrinol Metab 2008; 295: E785-E797
- 36 Huang H, Lee SH, Ye C, Lima IS, Oh BC, Lowell BB, Zabolotny JM, Kim YB. ROCK1 in AgRP neurons regulates energy expenditure and locomotor activity in male mice. Endocrinology 2013; 154: 3660-3670
- 37 Lian J, De Santis M, He M, Deng C. Risperidone-induced weight gain and reduced locomotor activity in juvenile female rats: The role of histaminergic and NPY pathways. Pharmacol Res 2015; 95–96: 20-26
- 38 Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 2003; 463: 3-33
- 39 Kopp C, Misslin R, Vogel E, Rettori MC, Delagrange P, Guardiola Lemaîre B. Effects of day-length variations on emotional responses toward unfamiliarity in Swiss mice. Behav Proc 1997; 41: 151-157
- 40 Kadmiel M, Cidlowski JA. Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci 2013; 34: 518-530
- 41 Ferreira VM, Takahashi RN, Morato GS. Dexamethasone reverses the ethanol-induced anxiolytic effect in rats. Pharmacol Biochem Behav 2000; 66: 585-590
- 42 Bhatt S, Shukla P, Raval J, Goswami S. Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats. Basic Clin Pharmacol Toxicol 2016; 119: 10-18
- 43 Pan Y, Lin W, Wang W, Qi X, Wang D, Tang M. The effects of central pro-and anti-inflammatory immune challenges on depressive-like behavior induced by chronic forced swim stress in rats. Behav Brain Res 2013; 247: 232-240