title: Emodin, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, regulates adipocyte function in vitro and exerts anti-diabetic effect in ob/ob mice.
abstract: OBJECTIVE
  Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-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. 11β-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⁻¹·d⁻¹, 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 11β-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 11β-HSD1 activity in mesenteric adipose tissues, lowered non-fasting and fasting blood glucose levels, and improved glucose tolerance.
  
  
  CONCLUSIONS
  Emodin improves the inactive glucocorticoid-induced adipose tissue dysfunction by selective inhibition on 11β-HSD1 in adipocyte in vitro and improves glycemic control in ob/ob mice.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: Yue-Jing
authors.initials: YJ
authors.lastname: Wang
authors.forename: Su-Ling
authors.initials: SL
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Ning
authors.forename: Ying
authors.initials: Y
authors.lastname: Leng
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005938:Glucocorticoids / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese; D013997:Time Factors
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D007328:Insulin; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D004642:Emodin