Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
Front Endocrinol (Lausanne). 2021 Mar 12;12:572690. doi: 10.3389/fendo.2021.572690. eCollection 2021.
The global obesity population is increasing year-by-year, and the related cost is sharply increasing annually. There are several methods available to combat obesity; however, there is a lack of a single tool that is both safe and efficacious. The use of Clenbuterol in bodybuilding and by professional athletes is controversial owing to its side effects, including hepatotoxicity. This study administered Clenbuterol at a much lower dose than the established safety level, and rather than through oral administration, the treatments were delivered through controlled-release intra-adipose injection. The different dosing and mode of administration will lower the risk of side effects, increase the safety profile, and could facilitate use in the anti-obesity market. A thermo-sensitive hydrogel was used as the carrier uploaded with Clenbuterol to achieve controlled-release. In the study, the developed new formulae were not cytotoxic to 3T3-L1 cells and could inhibit lipogenesis effectively. In the animal study, the mice were fed a high-fat diet and treated with Clenbuterol by oral administration, or injected with Clenbuterol-modified hyaluronate hydrogel (HAC) regularly. Both groups showed reduction in whole-body, visceral, and gonadal fat contents and body weight. The abdominal fat was analyzed using MRI imaging in adipose mode and water mode. The abdominal fat ratio in the mice treated with normal diet and those given intra-adipose injections with HAC had the lowest value among the test groups. The mice treated with high-fat diet (HFD) showed the highest value of 53.78%. The chronic toxicity test proved that controlled-release injections of 2-10 µg Clenbuterol daily were safe, as demonstrated in the blood elements and serological analyses. This study developed a new and promising method for anti-obesity treatment, using a monthly intra-adipose controlled-release injection of HAC. The developed new formulae of Clenbuterol not only effectively decreased body weight and body fat content but also inhibited lipogenesis on the harvested visceral tissue and reduced adipose tissue around the gonadal fat area. The side effects induced by traditional oral administration of Clenbuterol were not observed in this research; this has excellent potential to be a useful tool for future obesity treatment without safety concerns.
全球肥胖人口逐年增加，相关成本也在逐年急剧上升。有几种方法可以对抗肥胖，但缺乏一种既安全又有效的单一工具。由于其副作用，包括肝毒性，克伦特罗在健美和职业运动员中的使用存在争议。本研究以远低于既定安全水平的剂量给予克伦特罗，而不是通过口服给药，而是通过控制释放的皮下注射给药。不同的剂量和给药方式将降低副作用风险，提高安全性，并有助于在抗肥胖市场中使用。使用热敏感水凝胶作为载体上传克伦特罗以实现控释。在研究中，开发的新配方对 3T3-L1 细胞没有细胞毒性，并能有效抑制脂肪生成。在动物研究中，给高脂饮食喂养的小鼠口服给予克伦特罗或定期皮下注射克伦特罗修饰透明质酸水凝胶（HAC）。两组均能减少全身、内脏和性腺脂肪含量和体重。采用磁共振成像（MRI）在脂肪模式和水模式下分析腹部脂肪。在接受正常饮食和接受 HAC 皮下注射治疗的小鼠中，腹部脂肪比率在测试组中最低。接受高脂肪饮食（HFD）的小鼠的比率最高，为 53.78%。慢性毒性试验证明，每天 2-10μg 克伦特罗的控释注射是安全的，这在血液元素和血清学分析中得到了证明。本研究开发了一种新的、有前途的抗肥胖治疗方法，即每月皮下注射 HAC 控释。开发的新配方不仅能有效降低体重和体脂肪含量，还能抑制收获的内脏组织中的脂肪生成，并减少性腺脂肪区周围的脂肪组织。本研究未观察到传统口服克伦特罗引起的副作用；这具有极好的潜力成为一种安全有效的未来肥胖治疗工具。
