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.
Keywords: Gelatin; High-fat diet-induced obese rats; Microneedle; Subcutaneous adipose tissue.
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