AdipoRon:新型小分子脂联素受体激动剂
陈璐;龚凤英;朱惠娟;
摘要(Abstract)：
<正>随着社会经济的发展和人民生活水平的提高,肥胖人群的数量不断增加。肥胖会导致人体的糖脂代谢出现异常,这与糖尿病、心血管疾病、血脂紊乱、骨关节疾病、癌症等多种疾病有密切关系,严重影响了人们的生活质量和寿命[1]。尽管合理的饮食和适当的体育锻炼可以控制体重、改善胰岛素抵抗,对异常的糖脂代谢起到一定作用,但临床上仍需一些安全、有效的药物进行治疗。目前的减肥药物主要分为肠道胰脂酶活性抑制剂和作用于中枢神经系统的食欲抑制剂
关键词(KeyWords)：
AdipoRon;脂联素;肥胖;糖脂代谢;腺苷酸活化蛋白激酶
基金项目(Foundation): 国家自然科学基金(30540036、30600836、30771026、81370898、81471024);; 北京市自然科学基金(7082079);; 国家临床重点专科建设项目(WBYZ2011-873)
作者(Author):
陈璐;龚凤英;朱惠娟;
Email:
DOI:
参考文献(References)：
- [1]Gesta S,Tseng YH,Kahn CR.Developmental origin of fat:tracking obesity to its source[J].Cell,2007,131:242-256.
- [2]Poulton A,Nanan R.Drugs for the treatment of obesity[J].JAMA,2014,311:1807.
- [3]Balsan GA,Vieira JL,De Oliveira AM,et al.Relationship between adiponectin,obesity and insulin resistance[J].Rev Assoc Med Bras,2015,61:72-80.
- [4]Scherer PE,Williams S,Fogliano M,et al.A novel serum protein similar to C1q,produced exclusively in adipocytes[J].J Biol Chem,1995,270:26746-26749.
- [5]Li RC,Krishnamoorthy P,Derohannessian S,et al.Psoriasis is associated with decreased plasma adiponectin levels independently of cardiometabolic risk factors[J].Clin Exp Dermatol,2014,39:19-24.
- [6]Obeid S,Hebbard L.Role of adiponectin and its receptors in cancer[J].Cancer Biol Med,2012,9:213-220.
- [7]Pajvani UB,Hawkins M,Combs TP,et al.Complex distribution,not absolute amount of adiponectin,correlates with thiazolidinedione-mediated improvement in insulin sensitivity[J].J Biol Chem,2004,279:12152-12162.
- [8]Yamauchi T,Nio Y,Maki T,et al.Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions[J].Nat Med,2007,13:332-339.
- [9]Kahn BB,Alquier T,Carling D,et al.AMP-activated protein kinase:ancient energy gauge provides clues to modern understanding of metabolism[J].Cell Metab,2005,1:15-25.
- [10]Tsuchida A,Yamauchi T,Takekawa S,et al.Peroxisome proliferator-activated receptor(PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue:comparison of activation of PPARalpha,PPARgamma,and their combination[J].Diabetes,2005,54:3358-3370.
- [11]Matsunami T,Sato Y,Ariga S,et al.Regulation of oxidative stress and inflammation by hepatic adiponectin receptor 2 in an animal model of nonalcoholic steatohepatitis[J].Int J Clin Exp Pathol,2010,3:472-481.
- [12]Okada-Iwabu M,Yamauchi T,Iwabu M,et al.A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity[J].Nature,2013,503:493-499.
- [13]Mootha VK,Handschin C,Arlow D,et al.Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle[J].Proc Natl Acad Sci U S A,2004,101:6570-6575.
- [14]Lee J.Adipose tissue macrophages in the development of obesity-induced inflammation,insulin resistance and type 2 diabetes[J].Arch Pharm Res,2013,36:208-222.