Selective targeting of visceral adiposity by polycation nanomedicine.
Nat Nanotechnol
; 17(12): 1311-1321, 2022 12.
Article
in En
| MEDLINE
| ID: mdl-36456644
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adiposity
/
Nanomedicine
Limits:
Animals
Language:
En
Journal:
Nat Nanotechnol
Year:
2022
Document type:
Article
Affiliation country:
Estados Unidos