Metformin booster adipocyte-targeted gene therapy for the treatment of obesity and related metabolic syndromes

作     者：Jie Chen Jee Young Chung Huapan Fang Lin Lin Yong-Hee Kim Huayu Tian Xuesi Chen Jie Chen;Jee Young Chung;Huapan Fang;Lin Lin;Yong-Hee Kim;Huayu Tian;Xuesi Chen

作者机构：Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Department of BioengineeringInstitute for Bioengineering and Biopharmaceutical ResearchBK 21 Plus Future Biopharmaceutical Human Resources Training and Research TeamHanyang University133-791 SeoulRepublic of Korea 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2022年第65卷第4期

页      面：796-809页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China(2021YFB3800900) the National Natural Science Foundation of China(51925305,51873208,51973217,51520105004,51803210) Jilin Province Science and Technology Development Program(20180414027GH,20200201075JC,20210509005RQ) 

主　　题：FABP4/5 gene therapy insulin resistance metformin obesity 

摘      要：Obesity has become an important public problem that endangers human conditions and urgently needs to be solved. However,most weight-loss drugs on the market have little effect and are accompanied by adverse effects such as strokes and heart ***, we construct an adipocyte-targeting polypeptide-based gene carrier consisting of an adipocyte-targeting peptide and ptoluylsulfonyl arginine-modified polylysine(ATS-PLL-RT), which can specifically bind to the prohibitin of mature *** further construct a short hairpin RNA(shRNA) to simultaneously silence fatty acid binding proteins 4 and 5(shFABP4/5).FABPs are molecular chaperones for fatty acid metabolism and storage in cells. Moreover, we introduce metformin for combined therapy. First, the metformin combination can effectively improve the efficiency of gene transfection. In addition, metformin itself has an alleviating effect on diet-induced obesity and relevant metabolic diseases. The combination treatment of obese mice with ATS-PLL-RT/shFABP4/5 and metformin achieves body weight reduction and metabolic recovery. This study provides a potentially effective strategy for the clinical treatment of obesity as well as mitigating obesity-induced metabolic syndromes.