Min-Jung Park , Junhyeong Lee , Merc Emil Matienzo , Sangyi Lim , Keon Kim , Chang-Min Lee , Dong-il Kim
{"title":"Delivery of thermogenic genes to metabolic tissues: Effects on body weight and glucose tolerance","authors":"Min-Jung Park , Junhyeong Lee , Merc Emil Matienzo , Sangyi Lim , Keon Kim , Chang-Min Lee , Dong-il Kim","doi":"10.1016/j.trsl.2025.09.003","DOIUrl":null,"url":null,"abstract":"<div><div>Adaptive thermogenesis, particularly via the β3-adrenergic receptor (ADRB3)–protein kinase A catalytic subunit α (PKA Cα)–uncoupling protein 1 (UCP1) pathway, promotes energy expenditure and contributes to metabolic homeostasis, thereby establishing this pathway as a promising therapeutic target for metabolic disorders associated with excessive energy intake. In this study, we aimed to evaluate the therapeutic potential of adeno-associated virus (AAV)-mediated gene therapy targeting thermogenic pathways in metabolic tissues for the treatment of obesity-related dysfunctions. We demonstrated that adipocyte-specific overexpression of UCP1 improved glucose tolerance. Similarly, ADRB3 overexpression significantly enhanced glucose tolerance. Furthermore, ectopic expression of UCP1 in hepatocytes and myofibers also led to improved glucose tolerance. These findings highlight the potential of AAV-mediated gene therapy targeting the ADRB3–PKA Cα–UCP1 axis as a promising strategy for the treatment of obesity-associated metabolic disorders.</div></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"283 ","pages":"Pages 47-55"},"PeriodicalIF":5.9000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S193152442500091X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Adaptive thermogenesis, particularly via the β3-adrenergic receptor (ADRB3)–protein kinase A catalytic subunit α (PKA Cα)–uncoupling protein 1 (UCP1) pathway, promotes energy expenditure and contributes to metabolic homeostasis, thereby establishing this pathway as a promising therapeutic target for metabolic disorders associated with excessive energy intake. In this study, we aimed to evaluate the therapeutic potential of adeno-associated virus (AAV)-mediated gene therapy targeting thermogenic pathways in metabolic tissues for the treatment of obesity-related dysfunctions. We demonstrated that adipocyte-specific overexpression of UCP1 improved glucose tolerance. Similarly, ADRB3 overexpression significantly enhanced glucose tolerance. Furthermore, ectopic expression of UCP1 in hepatocytes and myofibers also led to improved glucose tolerance. These findings highlight the potential of AAV-mediated gene therapy targeting the ADRB3–PKA Cα–UCP1 axis as a promising strategy for the treatment of obesity-associated metabolic disorders.
期刊介绍:
Translational Research (formerly The Journal of Laboratory and Clinical Medicine) delivers original investigations in the broad fields of laboratory, clinical, and public health research. Published monthly since 1915, it keeps readers up-to-date on significant biomedical research from all subspecialties of medicine.