Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice
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 incr...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Journal of Nutrition and Metabolism |
| Online Access: | http://dx.doi.org/10.1155/2011/235389 |
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| author | Tomoko Asagami Joseph K. Belanoff Junya Azuma Christine M. Blasey Robin D. Clark Philip S. Tsao |
| author_facet | Tomoko Asagami Joseph K. Belanoff Junya Azuma Christine M. Blasey Robin D. Clark Philip S. Tsao |
| author_sort | Tomoko Asagami |
| collection | DOAJ |
| description | 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, high-sugar diet plus either mifepristone or CORT 108297 gained significantly less weight. At the end of the four week treatment period, mice receiving CORT 108297 40 mg/kg BID or CORT 108297 80 mg/kg QD also had significantly lower steady plasma glucose than mice receiving vehicle. However, steady state plasma glucose after treatment was not highly correlated with reduced weight gain, suggesting that the effect of the glucocorticoid receptor antagonist on insulin sensitivity may be independent of its mitigating effect on weight gain. |
| format | Article |
| id | doaj-art-d6bb35cb66ce4922b62ec2b2fdba9564 |
| institution | Kabale University |
| issn | 2090-0724 2090-0732 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nutrition and Metabolism |
| spelling | doaj-art-d6bb35cb66ce4922b62ec2b2fdba95642025-02-03T05:52:10ZengWileyJournal of Nutrition and Metabolism2090-07242090-07322011-01-01201110.1155/2011/235389235389Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in MiceTomoko Asagami0Joseph K. Belanoff1Junya Azuma2Christine M. Blasey3Robin D. Clark4Philip S. Tsao5Department of Cardiovascular Medicine, Stanford University, Stanford, CA 94305, USADepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USADepartment of Cardiovascular Medicine, Stanford University, Stanford, CA 94305, USADepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USACorcept Therapeutics, Menlo Park, CA 94025, USADepartment of Cardiovascular Medicine, Stanford University, Stanford, CA 94305, USAPrevious 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, high-sugar diet plus either mifepristone or CORT 108297 gained significantly less weight. At the end of the four week treatment period, mice receiving CORT 108297 40 mg/kg BID or CORT 108297 80 mg/kg QD also had significantly lower steady plasma glucose than mice receiving vehicle. However, steady state plasma glucose after treatment was not highly correlated with reduced weight gain, suggesting that the effect of the glucocorticoid receptor antagonist on insulin sensitivity may be independent of its mitigating effect on weight gain.http://dx.doi.org/10.1155/2011/235389 |
| spellingShingle | Tomoko Asagami Joseph K. Belanoff Junya Azuma Christine M. Blasey Robin D. Clark Philip S. Tsao Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice Journal of Nutrition and Metabolism |
| title | Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice |
| title_full | Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice |
| title_fullStr | Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice |
| title_full_unstemmed | Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice |
| title_short | Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice |
| title_sort | selective glucocorticoid receptor gr ii antagonist reduces body weight gain in mice |
| url | http://dx.doi.org/10.1155/2011/235389 |
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