Synergistic Treatment of Obesity via Locally Promoting Beige Adipogenesis and Antioxidative Defense in Adipose Tissues

文献类型： 外文期刊

第一作者： Ding, Zhenhua

作者： Ding, Zhenhua;Chen, Maohua;Tao, Xinyan;Liu, Yuan;He, Jie;Wang, Tao;Li, Xiaohong;Wang, Tao

作者机构：

关键词： obesity treatment; injectable short fibers; synergistic efficacy; beige adipogenesis; antioxidative defense

期刊名称：ACS BIOMATERIALS SCIENCE & ENGINEERING （ 影响因子：4.749； 五年影响因子：5.289 ）

ISSN： 2373-9878

年卷期： 2021 年 7 卷 2 期

页码：

收录情况： SCI

摘要： Obesity is a primary risk factor for type 2 diabetes, cardiovascular diseases, cancer, and other chronic diseases. Current antiobesity medications need frequent administration and show limited efficacy with severe side effects. Herein, browning agent rosiglitazone (Rsg) and antioxidant manganese tetroxide nanoparticles (MnNPs, around 250 nm) are integrated into electrospun short fibers (SF@Rsg-Mn) with a 1.5 mu m width and a 20 mu m length. Upon injection into inguinal adipose tissues, SF@Rsg-Mn are well retained in the local depots to sustainably release Rsg in 30 days for adipose tissue browning, while MnNPs on the fiber surface continuously scavenge adipose reactive oxygen species (ROS) for an extended period of time. Synergistic inhibition of fat accumulation through ROS scavenging and white adipocyte browning has been demonstrated for the first time, and the optimal synergistic ratio of Rsg and MnNPs is determined to be 1/14 via combination index examination. SF@Rsg-Mn inhibit lipid accumulation through downregulation of adipogenic gene PPAR gamma while promoting energy expenditure through upregulation of brown-specific gene UCP1 and mitochondrial function gene COX7A1. In a diet-induced obesity mouse model, a single injection of SF@Rsg-Mn into inguinal adipose tissues has accomplished a synergistic effect on body weight loss, fat reduction, glucose, and lipid metabolic improvement while minimizing adverse effects on other tissues, thereby paving the way to efficacious, safe, and practical treatment of obesity.

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