Selective targeting of visceral adiposity by polycation nanomedicine

Obesity 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. Moreover, 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. The visceral fat distribution of P-G3 is enhanced by modifying P-G3 with cholesterol to form lipophilic nanoparticles, which is effective in treating obesity. Our study highlights a strategy to target visceral adiposity and suggests that cationic nanomaterials could be exploited for treating metabolic diseases.

Automated summary

This research develops a nanomedicine based on polycation, which targets visceral fat selectively, preventing obesity and alleviating metabolic dysfunctions. By modulating nutrient-sensing signalling pathways, the polycation uncouples lipid synthesis and storage from adipocyte development, resulting in adipocytes with normal functions but deficient in hypertrophic growth. The study suggests the potential of cationic nanomaterials in treating metabolic diseases.