selective glucocorticoid receptor (gr-ii) antagonist reduces body weight gain in mice选择性糖皮质激素受体(gr-ii)拮抗剂减少小鼠的体重增加.pdfVIP

Hindawi Publishing Corporation Journal of Nutrition and Metabolism Volume 2011, Article ID 235389, 4 pages doi:10.1155/2011/235389 Research Article Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice Tomoko Asagami,1 Joseph K. Belanoff,2, 3 Junya Azuma,1 Christine M. Blasey,2, 3 Robin D. Clark,3 and Philip S. Tsao1 1 Department of Cardiovascular Medicine, Stanford University, Stanford, CA 94305, USA 2 Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA 3 Corcept Therapeutics, Menlo Park, CA 94025, USA Correspondence should be addressed to Christine M. Blasey, cblasey@ Received 7 March 2011; Revised 26 April 2011; Accepted 27 April 2011 Academic Editor: Maria Luz Fernandez Copyright © 2011 Tomoko Asagami et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Previous research has shown that mifepristone can prevent and reverse weight gain in animals and human subjects taking antipsychotic medications. This proof-of-concept study tested whether a more potent and selective glucocorticoid receptor antagonist could block dietary-induced weight gain and increase insulin sensitivity in mice. Ten-week-old, male, C57BL/6J mice were fed a diet containing 60% fat calories and water supplemented with 11% sucrose for 4 weeks. Groups (n = 8) received one of the following: CORT 108297 (80 mg/kg QD), CORT 108297 (40 mg/kg BID), mifepristone (30 mg/kg BID), rosiglitazone (10 mg/kg QD), or vehicle. Compared to mice receiving a high-fat, high-sugar diet plus vehicle, mice receiving a high-fat, h