Mifepristone (RU 486), a blocker of type II glucocorticoid and progestin receptors, reverses a dietary form of obesity.
The effect of mifepristone (RU 486), a blocker of type II glucocorticoid receptors on the development of obesity that follows the feeding of a high-fat (HF) diet to Osborne-Mendel (OM) rats, has been investigated. OM rats fed a HF diet gained more weight and had larger retroperitoneal and parametrial fat pads than OM rats fed a high-carbohydrate low-fat (LF) diet. RU 486 (30 mg.kg-1.day-1) for 14 days completely reversed the body weight gain and the increase in fat pad size of OM rats fed a HF diet. RU 486 had no effect on body weight of OM rats fed a LF diet, but did reduce fat pad weights. The data suggest that type II glucocorticoid receptor activity modulates body fat deposition and is essential for the development of obesity, although a minor role for progestin receptor activity cannot be ruled out.
Okada
S
S
Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808.
York
D A
DA
Bray
G A
GA
D000818:Animals; D003345:Corticosterone / Q000097:blood; D004041:Dietary Fats; D005260:Female; D015735:Mifepristone / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D051381:Rats; D011922:Rats, Mutant Strains; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*
D004041:Dietary Fats; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D015735:Mifepristone; D003345:Corticosterone