Effects of 11beta-hydroxysteroid dehydrogenase inhibitor on body weight and glucose tolerance in Sprague-Dawley rats fed with a high-fat diet.
OBJECTIVE
Many studies have shown that glucocorticoids play a crucial role in the development of obesity and insulin resistance. This study investigated the therapeutic effects of long-term inhibition of glucocorticoid activity on obesity and insulin resistance.


METHODS
Four-week-old male Sprague-Dawley (SD) rats were randomly fed with a high-fat diet (fat content accounting for 20% of total calorie) (control group, n=8) or with a high-fat diet along with glycyrrhetic acid (GE, 800 mg/L), an inhibitor of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) for 24 weeks (GE-treated group, n=9). The body weights and the amount of food intake were monitored weekly and daily, respectively. After 24 weeks of GE treatment, oral glucose tolerance tests were performed. Blood glucose was measured by glucose oxidase method. The levels of plasma glucocorticoids, insulin and leptin were measured with radioimmunoassay. The levels of serum cholesterol and triglyceride were determined with an automatic measuring analyzer.


RESULTS
The food intake amount decreased significantly in the GE-treated group from 6 weeks and body weight gain was markedly less from 8 weeks after GE administration compared with the control group. After 24 weeks of treatment, the plasma levels of leptin and insulin in GE-treated rats were significantly reduced compared with the control group. The serum levels of cholesterol and triglyceride decreased markedly compared with the control group and the levels of blood glucose were significantly lower 15, 30, 60 and 120 minutes after oral glucose load in the GE-treated group compared with the control group.


CONCLUSIONS
Long-term GE treatment may contribute to resisting diet-induced obesity and insulin resistance.
Liu
Zheng-Juan
ZJ
Department of Pediatrics, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, China. liuzj_1963@yahoo.com.cn
Bai
Jie
J
Wang
Yu-Chuan
YC
Yan
Dong
D
Wang
Xiao-Xia
XX
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D004041:Dietary Fats / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005938:Glucocorticoids / Q000502:physiology; D005951:Glucose Tolerance Test; D006034:Glycyrrhetinic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004041:Dietary Fats; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007328:Insulin; D020738:Leptin; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid