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 ex vivo 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.

中文翻译：

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明胶的皮内输送可诱导脂肪分解并抑制脂肪细胞的脂肪生成

由于对化妆品和医学应用的兴趣不断增长，减少局部皮下脂肪组织数量的治疗药物具有治疗肥胖症的潜力。然而，由于并发症的风险，诸如外科手术的常规方法受到限制。在这里，我们报告了一种简单有效的方法，可通过使用微针辅助天然聚合物的透皮递送来局部减少皮下脂肪组织（AT）。经过体外筛选测试后，选择明胶作为治疗性聚合物以减少AT的积累。一个体外研究表明，明胶处理后，分离的脂肪细胞中甘油的释放水平（作为脂解的指标）升高。另外，明胶抑制与脂肪生成相关的基因的表达水平。将明胶微针（GMN）贴剂应用于高脂饮食（HD）诱导的肥胖大鼠后，GMN施用部位的皮下AT量显着减少，这也得到了组织学分析和显微计算机断层扫描的证实。此外，在GMN处理的皮下AT中，脂肪生成相关基因被下调。这些发现表明，GMN贴片可诱导脂肪分解并同时抑制脂肪生成，从而减少皮下AT的沉积。这个使用GMN的平台可能会提供一种新的策略，以最小的并发症来治疗过多的皮下AT。

重要声明

（1）意义

这项工作报告了一种新的方法，该方法使用明胶制备的可溶性微针贴剂来局部减少皮下脂肪组织，从而能够抑制脂肪细胞中的脂肪生成和脂解作用的加速。与对照组相比，明胶微针贴片显示出局部皮下脂肪显着减少达60％，而总重量没有任何变化。

（2）科学影响

这是第一份证明经透皮途径给药的明胶具有直接抗肥胖作用的报道，以及天然聚合物治疗剂可局部减少皮下脂肪的可行性。我们相信，我们的工作将激发Acta Biomaterialia的跨学科读者，他们是对天然聚合物，药物递送和肥胖症感兴趣的人。