The increased prevalence of obesity is recognized as one of the most serious public health problems affecting millions of people. Although some anti-obesity drugs are currently licensed for use, these drugs involve diverse side effects such as diarrhea, vomiting, and low efficiency. Here we developed a safe and efficient biomaterials-based anti-obesity nanosystem (PCG-EPL/miR33agonist), which was formed with poly (citric acid)-glycerol-polylysine (PCG-EPL) and miR33 agonist by self-assembly. The PCG-EPL could efficiently load, protect and deliver the miR33 agonist into the adipocytes and decreased the obesity-related IL-1β expression in adipocytes in vitro. The high-fat diet induced obese rat model experiment showed that the PCG-EPL/miR33agonist via caudal vein injection effectively reduced the body weight by enhancing lipid metabolism and decreasing the inflammatory factors expressions (IL-1β, TNF-α and IL-6) in vivo, without suppressing the appetite of rat. Compared with the obese mice, mice in PCG-EPL/miR33 had higher average food intake but lower energy conversion rate. PCG-EPL/miR33agonist significantly inhibited the growth of adipocytes. Noteworthy, this weight loss strategy is not only safe and efficient, but also does not need diet control. Thus, PCG-EPL may serve as an ideal platform for RNA drug delivery in anti-obesity therapy, especially for those who need to lose weight but unable to autonomously control their diet.

肥胖症患病率上升被认为是影响数百万人的最严重的公共卫生问题之一。尽管某些抗肥胖药目前已获许可使用，但这些药物会引起多种副作用，例如腹泻，呕吐和低效。在这里，我们开发了一种安全有效的基于生物材料的抗肥胖纳米系统（PCG-EPL / miR33激动剂），该系统由聚（柠檬酸）-甘油-聚赖氨酸（PCG-EPL）和miR33激动剂通过自组装形成。PCG-EPL可以有效地负载，保护miR33激动剂并将其递送到脂肪细胞中，并在体外降低肥胖相关的肥胖相关IL-1β表达。高脂饮食诱导的肥胖大鼠模型实验表明PCG-EPL / miR33激动剂通过通过增强脂类代谢和降低炎症因子表达（IL-1β，TNF-α和IL-6）尾静脉注射有效地降低体重在体内，没有抑制大鼠的胃口。与肥胖小鼠相比，PCG-EPL / miR33小鼠的平均食物摄入量较高，但能量转化率较低。PCG-EPL / miR33激动剂可显着抑制脂肪细胞的生长。值得注意的是，这种减肥策略不仅安全有效，而且不需要饮食控制。因此，PCG-EPL可以作为抗肥胖疗法中RNA药物输送的理想平台，特别是对于那些需要减肥但无法自主控制饮食的人而言。