The glucocorticoid receptor: Cause of or cure for obesity?

American Journal of Physiology - Endocrinology and Metabolism

Volumn 310, Issue 4, 2016, Pages E249-E257

  John, Kezia ^a   Marino, Joseph S ^b   Sanchez, Edwin R ^a   Hinds, Terry D ^a  

^a MEDICAL COLLEGE OF OHIO   (United States)

^b UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE   (United States)

Author keywords

Adipogenesis; Adipose differentiation; Glucocorticoid receptor; Glucocorticoid receptor ; Glucocorticoid receptor ; Glucocorticoids; Lipolysis

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 1; CHAPERONE; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; GLUCOCORTICOID RECEPTOR BETA; MINERALOCORTICOID RECEPTOR; GLUCOCORTICOID RECEPTOR ALPHA;

ADIPOGENESIS; EXERCISE; FATTY LIVER; HORMONAL REGULATION; HORMONE ACTION; HORMONE RESISTANCE; HUMAN; LIPID STORAGE; LIPOLYSIS; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; ANIMAL; LIPID METABOLISM; LIPOGENESIS; METABOLISM;

ANIMALS; FATTY LIVER; GLUCOCORTICOIDS; HUMANS; LIPID METABOLISM; LIPOGENESIS; LIPOLYSIS; OBESITY; RECEPTORS, GLUCOCORTICOID; RECEPTORS, MINERALOCORTICOID;

EID: 84958524027     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00478.2015     Document Type: Review

References (73)

1. Adams M, Reginato MJ, Shao D, Lazar MA, Chatterjee VK. Transcriptional activation by peroxisome proliferator-activated receptor gamma is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J Biol Chem 272: 5128-5132, 1997.
2. Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237: 268-275, 1987.
3. Bamberger CM, Bamberger AM, de Castro M, Chrousos GP. Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans. J Clin Invest 95: 2435-2441, 1995.
4. Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, Chien KR, Koder A, Evans RM. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 4: 585-595, 1999.
5. Berson A, De Beco V, Letteron P, Robin MA, Moreau C, El Kahwaji J, Verthier N, Feldmann G, Fromenty B, Pessayre D. Steatohepatitisinducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology 114: 764-774, 1998.
6. Berthon BS, MacDonald-Wicks LK, Wood LG. A systematic review of the effect of oral glucocorticoids on energy intake, appetite, and body weight in humans. Nutr Res 34: 179-190, 2014.
7. Buettner R, Parhofer KG, Woenckhaus M, Wrede CE, Kunz- Schughart LA, Scholmerich J, Bollheimer LC. Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol 36: 485-501, 2006.
8. Campbell JE, Fediuc S, Hawke TJ, Riddell MC. Endurance exercise training increases adipose tissue glucocorticoid exposure: adaptations that facilitate lipolysis. Metabolism 58: 651-660, 2009.
9. Campbell JE, Kiraly MA, Atkinson DJ, D'Souza AM, Vranic M, Riddell MC. Regular exercise prevents the development of hyperglucocorticoidemia via adaptations in the brain and adrenal glands in male Zucker diabetic fatty rats. Am J Physiol Regul Integr Comp Physiol 299: R168-R176, 2010.
10. Caprio M, Feve B, Claes A, Viengchareun S, Lombes M, Zennaro MC. Pivotal role of the mineralocorticoid receptor in corticosteroidinduced adipogenesis. FASEB J 21: 2185-2194, 2007.
11. Carmen GY, Victor SM. Signalling mechanisms regulating lipolysis. Cell Signal 18: 401-408, 2006.
12. Chatzopoulou A, Roy U, Meijer AH, Alia A, Spaink HP, Schaaf MJ. Transcriptional and metabolic effects of glucocorticoid receptor alpha and beta signaling in zebrafish. Endocrinology 156: 1757-1769, 2015.
13. Choi JH, Banks AS, Estall JL, Kajimura S, Bostrom P, Laznik D, Ruas JL, Chalmers MJ, Kamenecka TM, Bluher M, Griffin PR, Spiegelman BM. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. Nature 466: 451-456, 2010.
14. Coutinho AE, Campbell JE, Fediuc S, Riddell MC. Effect of voluntary exercise on peripheral tissue glucocorticoid receptor content and the expression and activity of 11β-HSD1 in the Syrian hamster. J Appl Physiol 100: 1483-1488, 2006.
15. Dey A, Hao S, Erion JR, Wosiski-Kuhn M, Stranahan AM. Glucocorticoid sensitization of microglia in a genetic mouse model of obesity and diabetes. J Neuroimmunol 269: 20-27, 2014.
16. Divertie GD, Jensen MD, Miles JM. Stimulation of lipolysis in humans by physiological hypercortisolemia. Diabetes 40: 1228-1232, 1991.
17. Droste SK, Gesing A, Ulbricht S, Muller MB, Linthorst AC, Reul JM. Effects of long-term voluntary exercise on the mouse hypothalamicpituitary- adrenocortical axis. Endocrinology 144: 3012-3023, 2003.
18. DuBois DC, Sukumaran S, Jusko WJ, Almon RR. Evidence for a glucocorticoid receptor beta splice variant in the rat and its physiological regulation in liver. Steroids 78: 312-320, 2013.
19. Goedecke JH, Chorell E, Livingstone DE, Stimson RH, Hayes P, Adams K, Dave JA, Victor H, Levitt NS, Kahn SE, Seckl JR, Walker BR, Olsson T. Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women. Int J Obes 39: 303-311, 2015.
20. Goto T, Lee JY, Teraminami A, Kim YI, Hirai S, Uemura T, Inoue H, Takahashi N, Kawada T. Activation of peroxisome proliferator-activated receptor-alpha stimulates both differentiation and fatty acid oxidation in adipocytes. J Lipid Res 52: 873-884, 2011.
21. Grankvist N, Amable L, Honkanen RE, Sjoholm A, Ortsater H. Serine/threonine protein phosphatase 5 regulates glucose homeostasis in vivo and apoptosis signalling in mouse pancreatic islets and clonal MIN6 cells. Diabetologia 55: 2005-2015, 2012.
22. Grankvist N, Honkanen RE, Sjoholm A, Ortsater H. Genetic disruption of protein phosphatase 5 in mice prevents high-fat diet feeding-induced weight gain. FEBS Lett 587: 3869-3874, 2013.
23. Gray NE, Lam LN, Yang K, Zhou AY, Koliwad S, Wang JC. Angiopoietin-like 4 (Angptl4) protein is a physiological mediator of intracellular lipolysis in murine adipocytes. J Biol Chem 287: 8444-8456, 2012.
24. Hansen D, Meeusen R, Mullens A, Dendale P. Effect of acute endurance and resistance exercise on endocrine hormones directly related to lipolysis and skeletal muscle protein synthesis in adult individuals with obesity. Sports Med 42: 415-431, 2012.
25. Hinds TD Jr, Ramakrishnan S, Cash HA, Stechschulte LA, Heinrich G, Najjar SM, Sanchez ER. Discovery of glucocorticoid receptor-beta in mice with a role in metabolism. Mol Endocrinol 24: 1715-1727, 2010.
26. Hinds TD Jr, Sánchez ER. Protein phosphatase 5. Int J Biochem Cell Biol 40: 2358-2362, 2008.
27. Hinds TD Jr, Sodhi K, Meadows C, Fedorova L, Puri N, Kim DH, Peterson SJ, Shapiro J, Abraham NG, Kappas A. Increased HO-1 levels ameliorate fatty liver development through a reduction of heme and recruitment of FGF21. Obesity (Silver Spring) 22: 705-712, 2014.
28. Hinds TD Jr, Stechschulte LA, Cash HA, Whisler D, Banerjee A, Yong W, Khuder SS, Kaw MK, Shou W, Najjar SM, Sanchez ER. Protein phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid receptor and peroxisome proliferator-activated receptor- gamma (PPARgamma). J Biol Chem 286: 42911-42922, 2011.
29. Hinds TD, Stechschulte LA, Elkhairi F, Sanchez ER. Analysis of FK506, timcodar (VX-853) and FKBP51 and FKBP52 chaperones in control of glucocorticoid receptor activity and phosphorylation. Pharmacol Res Perspect 2: e00076, 2014.
30. Hoppmann J, Perwitz N, Meier B, Fasshauer M, Hadaschik D, Lehnert H, Klein J. The balance between gluco- and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol 204: 153-164, 2010.
31. Hu E, Kim JB, Sarraf P, Spiegelman BM. Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma. Science 274: 2100-2103, 1996.
32. Huizenga NA, de Lange P, Koper JW, de Herder WW, Abs R, Kasteren JH, de Jong FH, Lamberts SW. Five patients with biochemical and/or clinical generalized glucocorticoid resistance without alterations in the glucocorticoid receptor gene. J Clin Endocrinol Metab 85: 2076-2081, 2000.
33. Jacob W, Rosenzweig D, Vázquez-Martin C, Duce SL, Cohen PT. Decreased adipogenesis and adipose tissue in mice with inactivated protein phosphatase 5. Biochem J 466: 163-176, 2015.
34. Jenson M, Kilroy G, York DA, Braymer D. Abnormal regulation of hepatic glucocorticoid receptor mRNA and receptor protein distribution in the obese Zucker rat. Obes Res 4: 133-143, 1996.
35. Johannsson G, Ragnarsson O. Cardiovascular and metabolic impact of glucocorticoid replacement therapy. Front Horm Res 43: 33-44, 2014.
36. Kino T, Manoli I, Kelkar S, Wang Y, Su YA, Chrousos GP. Glucocorticoid receptor (GR) beta has intrinsic, GRalpha-independent transcriptional activity. Biochem Biophys Res Commun 381: 671-675, 2009.
37. Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 83: 813-819, 1995.
38. Krintel C, Morgelin M, Logan DT, Holm C. Phosphorylation of hormone- sensitive lipase by protein kinase A in vitro promotes an increase in its hydrophobic surface area. FEBS J 276: 4752-4762, 2009.
39. Kubota N, Terauchi Y, Miki H, Tamemoto H, Yamauchi T, Komeda K, Satoh S, Nakano R, Ishii C, Sugiyama T, Eto K, Tsubamoto Y, Okuno A, Murakami K, Sekihara H, Hasegawa G, Naito M, Toyoshima Y, Tanaka S, Shiota K, Kitamura T, Fujita T, Ezaki O, Aizawa S, Kadowaki T, et al. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance Mol Cell 4: 597-609, 1999.
40. Lan NC, Graham B, Bartter FC, Baxter JD. Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids. J Clin Endocrinol Metab 54: 332-342, 1982.
41. Lefterova MI, Haakonsson AK, Lazar MA, Mandrup S. PPARgamma and the global map of adipogenesis and beyond. Trends Endocrinol Metab 25: 293-302, 2014.
42. Luger A, Deuster PA, Kyle SB, Gallucci WT, Montgomery LC, Gold PW, Loriaux DL, Chrousos GP. Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training. N Engl J Med 316: 1309-1315, 1987.
43. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 107: 450-455, 1999.
44. Marzolla V, Armani A, Feraco A, De Martino MU, Fabbri A, Rosano G, Caprio M. Mineralocorticoid receptor in adipocytes and macrophages: a promising target to fight metabolic syndrome. Steroids 91: 46-53, 2014.
45. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS. A transgenic model of visceral obesity and the metabolic syndrome. Science 294: 2166-2170, 2001.
46. Mueller KM, Kornfeld JW, Friedbichler K, Blaas L, Egger G, Esterbauer H, Hasselblatt P, Schlederer M, Haindl S, Wagner KU, Engblom D, Haemmerle G, Kratky D, Sexl V, Kenner L, Kozlov AV, Terracciano L, Zechner R, Schuetz G, Casanova E, Pospisilik JA, Heim MH, Moriggl R. Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes steatosis and hepatocellular carcinoma in mice. Hepatology 54: 1398-1409, 2011.
47. Oakley RH, Cidlowski JA. Cellular processing of the glucocorticoid receptor gene and protein: new mechanisms for generating tissue-specific actions of glucocorticoids. J Biol Chem 286: 3177-3184, 2011.
48. Owen OE, Cahill GF Jr. Metabolic effects of exogenous glucocorticoids in fasted man. J Clin Invest 52: 2596-2605, 1973.
49. Penfornis P, Viengchareun S, Le Menuet D, Cluzeaud F, Zennaro MC, Lombès M. The mineralocorticoid receptor mediates aldosteroneinduced differentiation of T37i cells into brown adipocytes. Am J Physiol Endocrinol Metab 279: E386-E394, 2000.
50. Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 290: G852-G858, 2006.
51. Reul JM, de Kloet ER, van Sluijs FJ, Rijnberk A, Rothuizen J. Binding characteristics of mineralocorticoid and glucocorticoid receptors in dog brain and pituitary. Endocrinology 127: 907-915, 1990.
52. Reyer H, Ponsuksili S, Wimmers K, Murani E. Transcript variants of the porcine glucocorticoid receptor gene (NR3C1). Gen Comp Endocrinol 189: 127-133, 2013.
53. Rockall AG, Sohaib SA, Evans D, Kaltsas G, Isidori AM, Monson JP, Besser GM, Grossman AB, Reznek RH. Hepatic steatosis in Cushing's syndrome: a radiological assessment using computed tomography. Eur J Endocrinol 149: 543-548, 2003.
54. Rogerson FM, Dimopoulos N, Sluka P, Chu S, Curtis AJ, Fuller PJ. Structural determinants of aldosterone binding selectivity in the mineralocorticoid receptor. J Biol Chem 274: 36305-36311, 1999.
55. Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7: 885-896, 2006.
56. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4: 611-617, 1999.
57. Roth J, Qiang X, Marbán SL, Redelt H, Lowell BC. The obesity pandemic: where have we been and where are we going? Obes Res 12, Suppl 2: 88S-101S, 2004.
58. Shimizu N, Maruyama T, Yoshikawa N, Matsumiya R, Ma Y, Ito N, Tasaka Y, Kuribara-Souta A, Miyata K, Oike Y, Berger S, Schutz G, Takeda S, Tanaka H. A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling. Nat Commun 6: 6693, 2015.
59. Slavin BG, Ong JM, Kern PA. Hormonal regulation of hormonesensitive lipase activity and mRNA levels in isolated rat adipocytes. J Lipid Res 35: 1535-1541, 1994.
60. Stechschulte LA, Hinds TD Jr, Ghanem SS, Shou W, Najjar SM, Sanchez ER. FKBP51 reciprocally regulates GRα and PPARγ activation via the Akt-p38 pathway. Mol Endocrinol 28: 1254-1264, 2014.
61. Stechschulte LA, Hinds TD Jr, Khuder SS, Shou W, Najjar SM, Sanchez ER. FKBP51 controls cellular adipogenesis through p38 kinasemediated phosphorylation of GRα and PPARγ. Mol Endocrinol 28: 1265-1275, 2014.
62. Stechschulte LA, Wuescher L, Marino JS, Hill JW, Eng C, Hinds TD Jr. Glucocorticoid receptor β stimulates Akt1 growth pathway by attenuation of PTEN. J Biol Chem 289: 17885-17894, 2014.
63. Strissel KJ, Stancheva Z, Miyoshi H, Perfield JW 2nd, DeFuria J, Jick Z, Greenberg AS, Obin MS. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56: 2910-2918, 2007.
64. Sutanto W, de Kloet ER. Mineralocorticoid receptor ligands: biochemical, pharmacological, and clinical aspects. Med Res Rev 11: 617-639, 1991.
65. Syed AA, Irving JA, Redfern CP, Hall AG, Unwin NC, White M, Bhopal RS, Weaver JU. Association of glucocorticoid receptor polymorphism A3669G in exon 9beta with reduced central adiposity in women. Obesity 14: 759-764, 2006.
66. Villacorta L, Schopfer FJ, Zhang J, Freeman BA, Chen YE. PPARgamma and its ligands: therapeutic implications in cardiovascular disease. Clin Sci 116: 205-218, 2009.
67. Wang F, Mullican SE, DiSpirito JR, Peed LC, Lazar MA. Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARgamma. Proc Natl Acad Sci USA 110: 18656-18661, 2013.
68. Warrier M, Hinds TD Jr, Ledford KJ, Cash HA, Patel PR, Bowman TA, Stechschulte LA, Yong W, Shou W, Najjar SM, Sanchez ER. Susceptibility to diet-induced hepatic steatosis and glucocorticoid resistance in FK506-binding protein 52-deficient mice. Endocrinology 151: 3225-3236, 2010.
69. Wu C, Macleod I, Su AI. BioGPS and MyGene.info: organizing online, gene-centric information. Nucleic Acids Res 41: D561-D565, 2013.
70. Wu C, Orozco C, Boyer J, Leglise M, Goodale J, Batalov S, Hodge CL, Haase J, Janes J, Huss JW 3rd, Su AI. BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources. Genome Biol 10: R130, 2009.
71. Xiao X, Li H, Yang J, Qi X, Zu X, Yang J, Zhong J, Cao R, Liu J, Wen G. Wnt/beta-catenin signaling pathway and lipolysis enzymes participate in methylprednisolone induced fat differential distribution between subcutaneous and visceral adipose tissue. Steroids 84: 30-35, 2014.
72. Xu C, He J, Jiang H, Zu L, Zhai W, Pu S, Xu G. Direct effect of glucocorticoids on lipolysis in adipocytes. Mol Endocrinol 23: 1161- 1170, 2009.
73. Zennaro MC, Le Menuet D, Viengchareun S, Walker F, Ricquier D, Lombes M. Hibernoma development in transgenic mice identifies brown adipose tissue as a novel target of aldosterone action. J Clin Invest 101: 1254-1260, 1998.