Adipose tissue-targeted 11β-hydroxysteroid dehydrogenase type 1 inhibitor protects against diet-induced obesity

Endocrine Journal

Juanmin Zha¹  Hanmei Qi¹  Juan Liu¹  Lin Wu¹  Long Wang¹  Yujie Li¹  Shan Lv¹  Aisen Zhang¹  Jing Yu¹  Miao Hu¹  Peng Cheng¹  Wenjuan Di¹  Guoxian Ding¹  Xiao Zhang²  Yi Zhong³ 

[1] Department of Geratology, the First Hospital Affiliated to Nanjing Medical University, Nanjing, P.R.China;Department of Preventive Medicine, Feinberg School of Medicine Northwestern University, Chicago, USA;Department of Pharmaceutical Chemistry, China Pharmaceutical University, Nanjing, P.R.China

关键词: Adipose tissue;    11β-hydroxysteroid dehydrogenase type 1;    Blood glucose;    Metabolic syndrome;   

DOI  :  10.1507/endocrj.K10E-318

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(40)Cited-By(8)Current pharmacological treatments for obesity and metabolic syndrome have various limitations.Recently, adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of obesity and metabolic syndrome.Nevertheless, there is no adipose tissue-targeted 11β-HSD1 inhibitor available now.We sought to develop a new 11β-HSD1 pharmacological inhibitor that homes specifically to the white adipose tissue and aimed to investigate whether adipose tissue-targeted 11β-HSD1 inhibitor might decrease body weight gain and improve glucose tolerance in diet-induced obesity mice.BVT.2733, an 11β-HSD1 selective inhibitor was connected with a peptide CKGGRAKDC that homes to white fat vasculature.CKGGRAKDC-BVT.2733 (T-BVT) or an equimolar mixture of CKGGRAKDC and BVT.2733 (NT-BVT) was given to diet-induced obesity mice for two weeks through subcutaneous injection.T-BVT decreased body weight gain, improved glucose tolerance and decreased adipocyte size compared with vehicle treated mice.In adipose tissue T-BVT administration significantly increased adiponectin, vaspin mRNA levels; In liver T-BVT administration decreased the mRNA level of phosphoenolpyruvate carboxykinase (PEPCK), increased the mRNA levels of mitochondrial carnitine palmi-toyltransferase-I (mCPT-I) and peroxisome proliferator-activated receptorα(PPARα).No significant differences in adipocyte size and hepatic gene expression were observed after treatment with NT-BVT compared with vehicle treated mice, though NT-BVT also decreased body weight gain, improved glucose tolerance, and increased uncoupling protein-2 (UCP-2) mRNA levels in muscle.These results suggest that an adipose tissue-targeted pharmacological inhibitor of 11β-HSD1 may prove to be a new approach for the treatment of obesity and metabolic syndrome.

【 授权许可】

Unknown