Stearic acid-modified hexavanadate vesicles loaded with hydroxy fatty acid esters synergistically improve obesity-related metabolic disorders and inflammation

Obesity-driven insulin resistance and chronic inflammation present pressing therapeutic challenges, necessitating innovative strategies that target underlying metabolic dysregulation. Here, we report the development of stearic acid-modified hexavanadate (SA-V6) vesicles, a self-assembling nanoplatform engineered for efficient loading and delivery of Palmitic acid hydroxystearic acids (PAHSAs). In a high-fat diet (HFD)-induced murine obesity model, SA-V6/HFAE vesicles exhibited enhanced intestinal absorption, synergistically alleviating glucose-lipid metabolic disturbances via augmented insulin and glucagon-like peptide (GLP-1) secretion, as evidenced by improved glycemic control and normalized serum lipid profiles. Furthermore, the hybrid vesicles suppressed proinflammatory cytokine secretion in adipose tissue while activating the GPR120 and insulin signaling axis, a dual mechanism critical to restoring metabolic homeostasis. By integrating nanomaterial design with multifunctional bioactive cargo, this work establishes a promising therapeutic approach to address obesity-associated metabolic dysfunction and inflammation. The dual action of SA-V6/HFAE vesicles in enhancing insulin and GLP-1 secretion, alongside GPR120 pathway activation, highlights their potential as a translatable platform for precision management of complex metabolic disorders.