Abstract

Obesity caused by fat expansion is a pandemic health problem with poor solutions, especially for targeted treatment. Here we develop a polycation-based nanomedicine polyamidoamine generation 3 (P-G3) that—when delivered intraperitoneally—selectively targets visceral fat due to its high charge density. P-G3 treatment of obese mice inhibits visceral adiposity, increases energy expenditure, prevents obesity and alleviates the associated metabolic dysfunctions. In vitro adipogenesis models and single-cell RNA sequencing revealed that P-G3 uncouples adipocyte lipid synthesis and storage from adipocyte development to create adipocytes that possess normal functions but are deficient in hypertrophic growth, at least through synergistically modulating nutrient-sensing signalling pathways. We further engineered P-G3 into cargo carrier with improved visceral fat distribution. Moreover, we complexed P-G3 with human serum albumin (HSA) to attain a sustained release. Local injection of HSA-PG3 into subcutaneous fat completely restricted the distribution of the complex within the targeted depot and reduced focal adiposity. Our study highlights a cationic strategy to target fat in a depot-specific manner and suggests that cationic nanomaterials could be exploited for treating metabolic diseases.

Resume

Dr. Qiang is an Associate Professor with Tenure in the Department of Pathology and Cell Biology and the Naomi Berrie Diabetes Center at Columbia University. His laboratory focuses on the mechanisms of adipose remodeling in the pathophysiology of obesity and aging. He and his team have published in  Cell ,  Cell Metabolism ,  JCI ,  ACS Nano ,  J. of Hepatology ,  Nature Nanotechnology ,  Biomaterials ,  Diabetes ,  Advanced Sciences , etc. His finding of brown remodeling of white fat was among the year’s top ten notable advances in metabolism. He pioneers depot-specific targeting of fat for local obesity treatment. His findings on the selective activation of anti-diabetic drug target PPARg pave the way for the development of next-generation insulin sensitizers with improved safety. Dr. Qiang has received the NIH career development award with a perfect score and Kern Lipid Conference Early Investigator Award. He graduated from Peking University in 2001 and received his doctoral degree from Boston University School of Medicine in 2007.