The research team of the Li Ka Shing Faculty of Medicine of the University of Hong Kong (HKU Faculty of Medicine) has developed nanoparticles loaded with thyroxine (Thyroid hormone, TH). The severe side effects associated with systemic delivery of TH are expected to advance the development of treatments for obesity and its complications. The findings have been published in the journal Nature Communications (Click here to browse journal articles）。
HKU Faculty of Medicine research team develops nano drug delivery system to help treat obesity and atherosclerosis. Members of the research team include (from left) Dr Zhang Yaming, Dr Zhang Liyi, Wang Qin, Dr Wang Weiping, Dr Jin Leigang, Professor Xu Aimin and Dr Chen Kang.
Obesity can lead to life-threatening chronic diseases such as diabetes, cardiovascular disease and neurodegeneration. TH is a very old hormone that can promote energy expenditure and has certain potential for the treatment of obesity and its complications. Although researchers have made great efforts in the past few decades, clinical trials have not yet proved that chronic systemic injection of TH has a significant weight loss effect on obese patients. At the same time, due to the wide distribution of TH receptors, systemic injection of TH usually leads to a variety of serious side effects, including tachycardia, heart disease, muscle atrophy and osteoporosis. In addition, although adipose tissue and skeletal muscle are considered to be the two main target organs for TH to increase metabolic rate and promote energy expenditure, whether TH can exert its weight loss effect only through adipose tissue remains to be proved.
Research Methods and Results
The research team developed TH-loaded nanoparticles. By modifying fat-targeting polypeptides on the nanoparticles, TH can be selectively delivered to adipose tissue. Compared with systemic delivery of TH, this targeted “fat-targeted delivery” of TH can treat obesity and its complications more effectively without causing side effects on non-adipose tissue. Studies have also found that in terms of mechanism, fat-targeted delivery of TH can convert “bad” white fat into “good” brown fat, generate heat, promote metabolism, and consume energy. In contrast, systemic delivery of TH inhibited sympathetic input and failed to “brown” white fat. In addition, the study also found that the fat-targeted delivery of TH can alleviate hypercholesterolemia and atherosclerosis, and reduce the risk of coronary heart disease and ischemic stroke.
Significance
Professor Xu Aimin from the State Key Laboratory of Biomedical Technology at the University of Hong Kong and the Department of Internal Medicine, Faculty of Medicine, the University of Hong Kong pointed out: “This study is the first to demonstrate that targeted delivery of TH to adipose tissue through nanoparticles can safely and effectively treat obesity and related diseases. Cardiometabolic complications. This finding also answers a long-standing mystery: why systemic injection of TH fails to reduce body weight. The successful application of a fat-targeted nanodrug delivery strategy to solve this puzzle provides a basis for the use of TH in the treatment of common chronic Illness reignites hope.”
research team
The study was co-led by Prof. Aimin Tsui, Department of Internal Medicine, Department of Internal Medicine, Faculty of Medicine, HKU State Key Laboratory of Biomedical Technology, and Dr. Wang Weiping, Assistant Professor, Dr. Li Dak Sum Research Center and Department of Pharmacology and Pharmacy. Chen Kang, a postdoctoral researcher at the State Key Laboratory of Biomedical Technology of HKU and the Department of Internal Medicine, Faculty of Medicine, HKU, is the first author. Professor Eric Honoré from the University of Côte d’Azur, the National Center for Scientific Research and the Institute of Molecular and Cellular Pharmacology, and Professor Lin Xiaoling from the State Key Laboratory of Biomedical Technology and the Department of Internal Medicine, Faculty of Medicine, HKU are co-authors.
thank you
This research was supported by the Hong Kong Research Grants Council (AoE/M/707-18, Outstanding Research Grant (No. 17125317), Collaborative Research Grant (No. C7037-17W), National Natural Science Foundation of China (No. 82070860 and No. 82161138026) and the Health Research Fund (No. 08192146).
