The effects of combined glucocorticoid/mineralocorticoid receptor modulation (CORT118335) on energy balance, adiposity, and lipid metabolism in male rats.

The effects of combined glucocorticoid/mineralocorticoid receptor modulation (CORT118335) on energy balance, adiposity, and lipid metabolism in male rats. Am J Physiol Endocrinol Metab. 2019 May 21;: Authors: Nguyen ET, Berman S, Streicher J, Estrada CM, Caldwell JL, Ghisays V, Ulrich-Lai Y, Solomon MB Abstract Psychological stress and excess glucocorticoids are associated with metabolic and cardiovascular diseases. Glucocorticoids primarily act through mineralocorticoid (MR) and glucocorticoid receptors (GR), and compounds modulating these receptors show promise in mitigating metabolic and cardiovascular-related phenotypes. CORT118335 (GR/MR modulator) prevents high fat diet-induced weight gain and adiposity in mice, but the ability of this compound to reverse obesity-related symptoms is unknown. Adult male rats were subcutaneously administered CORT118335 (3mg/kg, 10mg/kg, or 30mg/kg) or vehicle once daily. A five-day treatment with CORT118335 at 30mg/kg induced weight loss on a chow diet by decreasing food intake. However, lower doses of the compound attenuated body weight gain primarily due to decreased calorific efficiency, as there were no significant differences in food intake compared to vehicle. Notably, the body weight effects of CORT118335 persisted during a 2-week treatment hiatus, suggesting prolonged effects of the compound. To our knowledge, we are the first to demonstrate a sustained effect of combined GR/MR modulation...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research