Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes. (December 2017)

• Record Type: Journal Article
• Authors: Yong, Seok-Beom; Song, Yoonsung; Kim, Yong-Hee
• Is Part Of: Biomaterials. Volume 148(2017)
• Page Start: 81
• Page End: 89
• Publication Date: 2017-12
• Subjects: Adipose tissue macrophage -- Visceral adipose tissue -- Anti-inflammatory gene delivery -- Targeted gene delivery; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2017.09.023
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Obesity is an increasingly prevalent global health problem. Due to its close relations with metabolic diseases and cancer, new therapeutic approaches for treating obesity and obesity-induced metabolic diseases are required. Visceral white adipose tissue (WAT) has been closely associated with obesity-induced inflammation and adipose tissue macrophages (ATMs) are responsible for obesity-induced inflammation by releasing inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6. TNF-α converting enzyme (TACE) is a transmembrane enzyme that induces the enzymatic cleavage and release of inflammatory cytokines. In this study, we developed a nonviral gene delivery system consisting of an oligopeptide (ATS-9R) that can selectively target visceral ATMs. In here we shows visceral adipose tissue-dominant inflammatory gene over-expressions in obese mouse and our strategy enabled the preferential delivery of therapeutic genes to visceral ATMs and successfully achieved ATM-targeted gene silencing. Finally, ATS-9R-mediated TACE gene silencing in visceral ATMs alleviated visceral fat inflammation and improved type 2 diabetes by reducing whole body inflammation.