The effects of the acute administration of RU 486 on dietary fat preference in fasted lean and obese men

Abstract

The effects of RU 486, a potent glucocorticoid antagonist, on dietary fat preference were explored in obese men and lean controls in a double-blind crossover study. An oral 10 mg/kg dose of RU 486 or placebo was administered at midnight the second night of a 48-h hospital stay. Macronutrient and caloric intakes were calculated each day and a taste test of six commercial dairy products (fat content by weight <0.5%, 2.0%, 3.3%, 10.5%, 18%, and 36%) was performed. Dairy products were judged for pleasantness, creaminess, and overall preference. Subjects were then asked to consume their favorite dairy product until sated. Urinary free cortisol (UFC) and plasma adrenocorticotropic hormone (ACTH), cortisol, insulin, and glucose were determined. Intake of a self-selected diet was recorded. As expected, in response to RU 486, UFC increased from 120 ± 25 μg/24 h to 297 ± 73 μg/24 h ( p < 0.05) in obese men and from 81 ± 10 μg/24 h to 357 ± 109 μg/24 h ( p < 0.05) in lean men. Plasma cortisol increased from 26.1 ± 1.1 μg/dl to 31.8 ± 1.0 μg/dl ( p < 0.05) in obese men and from 26.1 ± 1.7 μg/dl to 32.2 ± 1.7 μg/dl ( p < 0.05) in lean men. Plasma insulin was significantly higher in obese 24.6 ± 3.2 μIU/ml than in lean men 12.8 ± 1.1 μIU/ml ( p = 0.0001) but was unaffected by RU 486. RU 486 did not decrease fat intake in either obese or lean men. However, in obese men UFC was significantly correlated with fat intake from the overall preferred product in the taste test ( r = 0.84, p < 0.05) and with fat intake during the following 24 h. This correlation was lost after RU 486 administration in obese men and was not seen in either condition in lean men. Although RU 486 did not alter fat intake in obese or lean men, correlations between UFC and both measures of fat intake in obese men suggest that cortisol may play a role in the pathophysiology of obesity.