Exploiting Spinach-Derived Extracellular Vesicles for Anti-Obesity Therapy Through Lipid Accumulation Inhibition

Obesity is a global health crisis, necessitating the development of biomaterial-based treatments as alternatives to conventional chemical medications with adverse effects. Extracellular vesicles (EVs), nanosized lipid membrane vesicles containing bioactive components, have emerged as promising biomaterials owing to their biocompatibility, biodistribution, and minimal immune response. Although EVs have been extensively studied for anticancer and anti-inflammatory properties, their potential for obesity therapy remains relatively unexplored. In this study, the therapeutic potential of spinach-derived EVs (Spinex) against obesity is investigated. Spinex is successfully purified from spinach using size exclusion chromatography. Subsequent assessments reveals that Spinex efficiently penetrate preadipocytes without cytotoxicity. Stability assessments reveals that Spinex is stable under various temperatures and serum conditions, suggesting its suitability for storage and clinical use. In vitro studies on 3T3-L1 cells demonstrate the ability of Spinex to suppress lipid accumulation during adipocyte differentiation. In a high-fat diet-induced mouse model, oral Spinex administration significantly reduces adipose tissue weight and body weight gain by downregulating key adipogenic transcription factors. Biodistribution analysis reveals that Spinex accumulated predominantly in the liver, with no apparent toxicity to the major organs. Collectively, the findings highlight Spinex as a promising natural biomaterial for combating obesity and pave the way for further clinical investigations.