Functional louts leaf extracellular vesicles for targeted delivery of curcumin through PPAR against obesity

Obesity is a serious global epidemic and is a risk factor for diseases such as cancer and cardiovascular disease, having a profound negative impact on human health. Obesity is caused by factors such as adipocyte differentiation, lipolysis, and cell cycle, and the number of fat cells continues to increase, ultimately leading to obesity. Curcumin (cur) is a food additive that has a role in obesity control and is a safe and effective active molecule for the treatment of obesity. However low solubility and rapid metabolic clearance limit its bioavailability. Plant-derived extracellular vesicles (PDEVs) are phospholipid bilayer nanostructures produced by living cells that can inherit parent cell bioactive molecules, mediate cell-to-cell information transfer, and have received widespread attention in the biopharmaceutical field. Therefore, we used lotus leaf extracellular vesicles (LEVs) as carriers and further modified them with adipo-8 to target cur for the treatment of obesity. In the obesity model, adipo-8-LEVs-cur was well targeted to the adipose tissue of mice. Mechanistically, adipo-8-LEVs-cur inhibited lipid droplet formation by downregulating the gene expression levels of adipogenesis-related factors peroxisome proliferator activated receptor gamma (PPARγ), CCAAT enhancer binding protein alpha (C/EBPα), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Additionally, adipo-8-LEVs-cur inhibited oxidative stress caused by fat production, alleviated mitochondrial damage, and improved blood lipid levels. In addition, adipo-8-LEVs-cur did not cause any damage to other organs. These results suggest that the adipo-8-LEVs-cur delivery system provides an idea for obesity treatment targeting adipocytes, which is of practical significance for anti-obesity research.