RESUMO
AIM: Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a potent and selective inhibitor of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) with the ability to ameliorate metabolic disorders in diet-induced obese mice. In the present study, we investigated the effects of emodin on adipocyte function and the underlying mechanisms in vitro, and its anti-diabetic effects in ob/ob mice. METHODS: 3T3-L1 adipocytes were used for in vitro studies. 11ß-HSD1A activity was evaluated with a scintillation proximity assay. The adipogenesis, glucose uptake, lipolysis and adiponectin secretion were investigated in 3T3-L1 adipocytes treated with emodin in the presence of active (corticosterone) or inactive glucocorticoid (11-dehydrocorticosterone). For in vivo studies, ob/ob mice were administered emodin (25 and 50 mg·kg⻹·d⻹, ip) for 26 d. On the last day of administration, the serum was collected and the mesenteric and perirenal fat were dissected for analyses. RESULTS: Emodin inhibited the 11ß-HSD1 activity in 3T3-L1 adipocytes in concentration- and time-dependent manners (the IC50 values were 7.237 and 4.204 µmol/L, respectively, after 1 and 24 h treatment. In 3T3-L1 adipocytes, emodin (30 µmol/L) suppressed 11-dehydrocorticosterone-induced adipogenesis without affecting corticosterone-induced adipogenesis; emodin (3 µmol/L) reduced 11-dehydrocorticosterone-stimulated lipolysis, but had no effect on corticosterone-induced lipolysis. Moreover, emodin (3 µmol/L) partly reversed the impaired insulin-stimulated glucose uptake and adiponectin secretion induced by 11-dehydrocorticosterone but not those induced by corticosterone. In ob/ob mice, long-term emodin administration decreased 11ß-HSD1 activity in mesenteric adipose tissues, lowered non-fasting and fasting blood glucose levels, and improved glucose tolerance. CONCLUSION: Emodin improves the inactive glucocorticoid-induced adipose tissue dysfunction by selective inhibition on 11ß-HSD1 in adipocyte in vitro and improves glycemic control in ob/ob mice.
