Related Experiment Video
Updated: May 30, 2026
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice
Tomoko Asagami1, Joseph K Belanoff, Junya Azuma
1Department of Cardiovascular Medicine, Stanford University, Stanford, CA 94305, USA.
Abstract:
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.
Insights
A novel glucocorticoid receptor antagonist, CORT 108297, effectively reduced weight gain and improved glucose levels in mice on a high-fat, high-sugar diet. This suggests potential for treating metabolic dysfunction associated with such diets.
Area of Science:
- Metabolic research
- Pharmacology
- Endocrinology
Background:
- Antipsychotic medications can cause weight gain.
- Mifepristone has previously shown efficacy in preventing and reversing weight gain.
- Glucocorticoid receptor antagonists are being investigated for metabolic benefits.
Purpose of the Study:
- To evaluate a potent glucocorticoid receptor antagonist (CORT 108297) for its ability to prevent diet-induced weight gain.
- To assess the impact of CORT 108297 on insulin sensitivity.
- To compare CORT 108297 with mifepristone and rosiglitazone in a mouse model.
Main Methods:
- Male C57BL/6J mice were fed a high-fat, high-sugar diet for 4 weeks.
- Treatment groups received CORT 108297 (80 mg/kg QD or 40 mg/kg BID), mifepristone (30 mg/kg BID), rosiglitazone (10 mg/kg QD), or vehicle.
- Body weight and plasma glucose levels were monitored.
Main Results:
- Mice treated with CORT 108297 or mifepristone exhibited significantly less weight gain compared to vehicle controls.
- CORT 108297 treatment resulted in significantly lower steady plasma glucose levels.
- Reduced weight gain and improved insulin sensitivity appeared to be independent effects.
Conclusions:
- CORT 108297 is effective in mitigating diet-induced weight gain in mice.
- This compound also improves glucose homeostasis, suggesting a role in enhancing insulin sensitivity.
- Glucocorticoid receptor antagonism may offer a therapeutic strategy for metabolic disorders.
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