Different responsiveness in body weight and hepatic 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 mrna to 11β-HSD inhibition by glycyrrhetinic acid treatment in obese and lean zucker rats

Abstract Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity in obese humans and animals may be associated with obesity and the metabolic syndrome. We investigated the effect of inhibition of 11β-HSD with glycyrrhetinic acid (GE), an effective 11β-HSD inhibitor, on body weight regulation in obese Zucker rats, which have a defect in the leptin receptor gene. GE (280 mg/kg/d) was administered in drinking water to 8-week-old male Zucker rats for 14 weeks. GE had no effect on food intake or weight gain, and did not affect hepatic 11β-HSD1 and renal 11β-HSD2 mRNA levels in obese rats. In contrast, average daily food intake and body weight on week 14 were significantly reduced by GE in lean rats (both P P P P