Abstract

 Obesity is characterized by chronic low-grade inflammation that originates primarily in expanding white 
adipose tissue and propagates to liver, skeletal muscle, vascular endothelium and pancreas, driving insulin 
resistance and cardiometabolic complications. Hypertrophic adipocytes and infiltrating immune cells, especially 
adipose tissue macrophages, sustain a network of inflammatory pathways centered on NF-κB, JNK and the 
NLRP3 inflammasome, with strong crosstalk to autophagy and metabolic signaling. Nanoparticles interact 
intimately with immune and stromal cells in these tissues, and can either exacerbate or resolve inflammatory 
stress depending on their composition, size, surface chemistry and cargo. This review summarizes the 
inflammatory biology of obesity and identifies key signaling nodes that are susceptible to nanoparticle-mediated 
modulation. We discuss lessons from nanotoxicology, where unintentionally pro-inflammatory nanomaterials 
highlight crucial design pitfalls, and then focus on rationally engineered anti-inflammatory nanotherapeutics 
targeting adipose tissue macrophages, adipocytes and systemic metabolic organs. Emerging platforms include 
drug- and nutraceutical-loaded nanoparticles that reprogram macrophage polarization, silence inflammasome 
signaling and couple inflammation resolution with adipose browning. Finally, we examine translational 
challenges regarding safety, targeting, regulation and personalization, and propose design principles for future 
immunometabolic nanotherapies in obesity.