Apigenin-loaded nanoparticles for obesity intervention through immunomodulation and adipocyte browning

Obesity is characterized by a significant imbalance in adipose tissue macrophages (ATMs), shifting from anti-inflammatory M2 to pro-inflammatory M1 phenotypes, contributing to chronic low-grade inflammation and metabolic dysfunction. This study explores the potential of nanoparticle (NP)-mediated immunomodulation to address obesity-related inflammation, adipocyte browning, and metabolic dysfunction. Apigenin (Api), a natural compound with notable anti-inflammatory properties, was encapsulated within poly(lactic-co-glycolic acid) (PLGA) NPs (Api-NPs) for localized delivery to adipose tissues (ATs). Api-NPs demonstrated favorable physicochemical properties and sustained release profiles. In vitro, Api-NPs, increased M2 macrophage (MΦ) polarization, reduced inflammatory markers, and promoted adipocyte browning. In a high-fat diet (HFD)-induced obesity mouse model, Api-NP administration effectively modulated MΦ polarization and enhanced AT browning, leading to marked reductions in body weight and AT mass. Our findings indicate that Api-NP treatment mitigates obesity-related inflammation and promotes beneficial changes in AT composition and function. Importantly, histological evaluations confirmed the absence of toxicity in major organs, reinforcing the safety profile of this approach. These results position Api-NPs as a promising novel therapeutic strategy for obesity management, integrating immune modulation and localized drug delivery to address the complexities of obesity and its associated inflammatory processes.