title: BVT.2733, a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, attenuates obesity and inflammation in diet-induced obese mice.
abstract: BACKGROUND
  Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is being pursued as a new therapeutic approach for the treatment of obesity and metabolic syndrome. Therefore, there is an urgent need to determine the effect of 11β-HSD1 inhibitor, which suppresses glucocorticoid action, on adipose tissue inflammation. The purpose of the present study was to examine the effect of BVT.2733, a selective 11β-HSD1 inhibitor, on expression of pro-inflammatory mediators and macrophage infiltration in adipose tissue in C57BL/6J mice.
  
  
  RESULTS
  C57BL/6J mice were fed with a normal chow diet (NC) or high fat diet (HFD). HFD treated mice were then administrated with BVT.2733 (HFD+BVT) or vehicle (HFD) for four weeks. Mice receiving BVT.2733 treatment exhibited decreased body weight and enhanced glucose tolerance and insulin sensitivity compared to control mice. BVT.2733 also down-regulated the expression of inflammation-related genes including monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α) and the number of infiltrated macrophages within the adipose tissue in vivo. Pharmacological inhibition of 11β-HSD1 and RNA interference against 11β-HSD1 reduced the mRNA levels of MCP-1 and interleukin-6 (IL-6) in cultured J774A.1 macrophages and 3T3-L1 preadipocyte in vitro.
  
  
  CONCLUSIONS
  These results suggest that BVT.2733 treatment could not only decrease body weight and improve metabolic homeostasis, but also suppress the inflammation of adipose tissue in diet-induced obese mice. 11β-HSD1 may be a very promising therapeutic target for obesity and associated disease.
authors: Department of Geratology, the First Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
authors: Long
authors: L
authors: Wang
authors: Juan
authors: J
authors: Liu
authors: Aisen
authors: A
authors: Zhang
authors: Peng
authors: P
authors: Cheng
authors: Xiao
authors: X
authors: Zhang
authors: Shan
authors: S
authors: Lv
authors: Lin
authors: L
authors: Wu
authors: Jing
authors: J
authors: Yu
authors: Wenjuan
authors: W
authors: Di
authors: Juanmin
authors: J
authors: Zha
authors: Xiaocen
authors: X
authors: Kong
authors: Hanmei
authors: H
authors: Qi
authors: Yi
authors: Y
authors: Zhong
authors: Guoxian
authors: G
authors: Ding
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004032:Diet / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005938:Glucocorticoids / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000096926:Benzenesulfonamides
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D018836:Inflammation Mediators; D010879:Piperazines; D013449:Sulfonamides; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C474501:3-chloro-2-methyl-N-(4-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-1,3-thiazol-2-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C491768:Ccl2 protein, mouse