Graduate School of Health, University of Technology Sydney, Chippendale, NSW 2008, Australia.
Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW 2037, Australia.
Int J Mol Sci. 2020 Oct 15;21(20):7640. doi: 10.3390/ijms21207640.
Current therapeutic options for obesity often require pharmacological intervention with dietary restrictions. Obesity is associated with underlying inflammation due to increased tissue macrophage infiltration, and recent evidence shows that inflammation can drive obesity, creating a feed forward mechanism. Therefore, targeting obesity-induced macrophage infiltration may be an effective way of treating obesity. Here, we developed cargo-less liposomes (UTS-001) using 1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC (synthetic phosphatidylcholine) as a single-agent to manage weight gain and related glucose disorders due to high fat diet (HFD) consumption in mice. UTS-001 displayed potent immunomodulatory properties, including reducing resident macrophage number in both fat and liver, downregulating liver markers involved in gluconeogenesis, and increasing marker involved in thermogenesis. As a result, UTS-001 significantly enhanced systemic glucose tolerance in vivo and insulin-stimulated cellular glucose uptake in vitro, as well as reducing fat accumulation upon ad libitum HFD consumption in mice. UTS-001 targets tissue residence macrophages to suppress tissue inflammation during HFD-induced obesity, resulting in improved weight control and glucose metabolism. Thus, UTS-001 represents a promising therapeutic strategy for body weight management and glycaemic control.
目前治疗肥胖症的方法通常需要药物干预和饮食限制。肥胖症与组织巨噬细胞浸润增加引起的潜在炎症有关,最近的证据表明炎症可以导致肥胖症,形成正反馈机制。因此,靶向肥胖诱导的巨噬细胞浸润可能是治疗肥胖症的有效方法。在这里,我们使用 1,2-二油酰基-sn-甘油-3-磷酸胆碱(DOPC)作为单一试剂,开发了无载药脂质体(UTS-001),以管理由于高脂肪饮食(HFD)消耗而导致的体重增加和相关葡萄糖紊乱在小鼠中。UTS-001 显示出强大的免疫调节特性,包括减少脂肪和肝脏中常驻巨噬细胞的数量,下调参与糖异生的肝脏标志物,并增加参与产热的标志物。结果,UTS-001 显著增强了体内的全身葡萄糖耐量和体外胰岛素刺激的细胞葡萄糖摄取,并减少了小鼠自由进食 HFD 时的脂肪积累。UTS-001 靶向组织驻留巨噬细胞,以抑制 HFD 诱导的肥胖症期间的组织炎症,从而改善体重控制和葡萄糖代谢。因此,UTS-001 代表了一种有前途的体重管理和血糖控制治疗策略。