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

Obesity-induced insulin resistance and chronic inflammation pose considerable therapeutic challenges, requiring innovative approaches to address the underlying metabolic dysregulation. We have developed stearic acid-modified hexavanadate (SA-V6) vesicles, a self-assembling nanoplatform designed for efficient loading and delivery of palmitic acid hydroxystearic acids (PAHSAs). In a murine model of high-fat diet (HFD)-induced obesity, SA-V6/PAHSA vesicles demonstrated increased intestinal absorption, leading to a synergistic alleviation of glucose–lipid metabolic disturbances through increased secretion of insulin and glucagon-like peptide (GLP-1), resulting in improved glycemic control and normalized serum lipid profiles. Additionally, the hybrid vesicles suppressed the secretion of proinflammatory cytokines in adipose tissue while activating the GPR120 and insulin signaling pathways, a dual mechanism crucial for restoring metabolic homeostasis. By combining nanomaterial design with multifunctional bioactive cargo, this study introduces a promising therapeutic strategy to address obesity-related metabolic dysfunction and inflammation. The dual effect of SA-V6/PAHSA vesicles, which increase insulin and GLP-1 secretion while activating the GPR120 pathway, underscores their potential as a translatable platform for accurate management of complex metabolic disorders.