Different responsiveness in body weight and hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 mrna to 11beta-HSD inhibition by glycyrrhetinic acid treatment in obese and lean zucker rats.
Tissue-specific dysregulation of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity in obese humans and animals may be associated with obesity and the metabolic syndrome. We investigated the effect of inhibition of 11beta-HSD with glycyrrhetinic acid (GE), an effective 11beta-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 11beta-HSD1 and renal 11beta-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 <.0001). Hepatic 11beta-HSD1 and renal 11beta-HSD2 mRNA levels were also significantly decreased by GE in lean rats (both P <.05). GE had no significant effect on plasma corticosterone levels in obese rats but lowered them in lean rats (P <.05). Plasma leptin levels declined in both GE-treated obese and lean rats (both P <.01). In conclusion, long-term GE treatment decreased weight gain in lean Zucker rats but not in obese Zucker rats. These findings suggest that the differing responses of 11beta-HSD1 to GE in obese and lean Zucker rats are closely associated with the different weight-gain responses. Furthermore, the weight-lowering effect of GE may require intact leptin receptors.
Li
Ren-Shan
RS
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Nakagawa
Yuichi
Y
Nakanishi
Toshiki
T
Fujisawa
Yasuko
Y
Ohzeki
Takehiko
T
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D007527:Isoenzymes; D007668:Kidney / Q000201:enzymology; D020738:Leptin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009765:Obesity / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker
D007527:Isoenzymes; D020738:Leptin; D012333:RNA, Messenger; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; D003345:Corticosterone