Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea.
Department of Plastic and Reconstructive Surgery, Pusan National University, Busan 46241, Republic of Korea.
Acta Biomater. 2018 Feb;67:238-247. doi: 10.1016/j.actbio.2017.11.050. Epub 2017 Dec 5.
Due to growing interest in cosmetics and medical applications, therapeutic medications that reduce the amount of local subcutaneous adipose tissue have potential for obesity treatment. However, conventional methods such as surgical operation are restricted due to risk of complications. Here, we report a simple and effective method for local reduction of subcutaneous adipose tissue (AT) by using microneedle-assisted transdermal delivery of natural polymers. After in vitro screening tests, gelatin was selected as a therapeutic polymer to reduce accumulation of AT. An in vitro study showed that the level of released glycerol as an indicator of lipolysis was elevated in isolated adipocytes after gelatin treatment. In addition, gelatins suppressed expression levels of lipogenesis-associated genes. Following application of gelatin microneedle (GMN) patches to high-fat diet (HD)-induced obese rats, the amount of subcutaneous AT at the site of GMN application was significantly reduced, which was also confirmed by histological analysis and micro-computed tomography scanning. In addition, lipogenesis-associated genes were down-regulated in GMN-treated subcutaneous AT. These findings suggest that GMN patches induce lipolysis and simultaneously inhibit lipogenesis, thereby reducing deposition of subcutaneous AT. This platform using GMNs may provide a new strategy to treat excess subcutaneous AT with minimal complications. STATEMENT OF SIGNIFICANCE: (1) Significance This work reports a new approach for the local reduction of subcutaneous adipose tissue using a dissolving microneedle patch prepared using gelatin to enable suppression of lipogenesis and acceleration of lipolysis in adipocytes. The gelatin microneedle patch exhibited a significant reduction of local subcutaneous fat up to 60% compared to control groups without any change in total weight. (2) Scientific impact This is the first report demonstrating the direct anti-obesity effects of gelatin administrated in a transdermal route and the feasibility of natural polymer therapeutics for regional reduction of subcutaneous fat. We believe that our work will excite interdisciplinary readers of Acta Biomaterialia, those who are interested in the natural polymers, drug delivery, and obesity.
由于人们对化妆品和医学应用的兴趣日益浓厚，减少局部皮下脂肪组织的治疗性药物有可能用于肥胖症的治疗。然而，由于存在并发症的风险，传统的方法如手术受到限制。在这里，我们报告了一种通过使用微针辅助经皮递送天然聚合物来局部减少皮下脂肪组织（AT）的简单有效的方法。经过体外筛选测试，选择明胶作为治疗性聚合物来减少 AT 的积累。体外研究表明，明胶处理后分离的脂肪细胞中甘油释放水平升高，作为脂肪分解的指标。此外，明胶抑制了与脂肪生成相关的基因的表达水平。在将明胶微针（GMN）贴片应用于高脂肪饮食（HD）诱导的肥胖大鼠后，GMN 应用部位的皮下 AT 量明显减少，组织学分析和微计算机断层扫描扫描也证实了这一点。此外，GMN 处理的皮下 AT 中与脂肪生成相关的基因下调。这些发现表明，GMN 贴片诱导脂肪分解，同时抑制脂肪生成，从而减少皮下 AT 的沉积。该使用 GMN 的平台为通过最小化并发症来治疗过多的皮下 AT 提供了一种新策略。
