Nanosphere loaded with curcumin attenuates adipogenesis and lipid metabolism by modulating AKT/mTORC1/PPARγ phosphorylation

Curcumin, a hydrophobic polyphenol derived from turmeric, exhibits diverse biological activities as a natural supplement. However, its low gastrointestinal absorption significantly limits its oral bioavailability. In this study, we investigated the effects of curcumin-loaded nanospheres (CN) on adipocyte differentiation in 3T3-L1 cells and obesity development in high-fat diet-induced obese mice. CN markedly suppressed adipogenesis in 3T3-L1 preadipocytes, demonstrating approximately 100-fold greater anti-adipogenic activity compared to native curcumin. Mechanistically, CN inhibited mTOR phosphorylation by modulating intracellular reactive oxygen species during adipocyte differentiation. Notably, CN restored fatty acid synthase expression through regulation of PPARγ phosphorylation. In high-fat diet-fed mice, oral administration of CN significantly reduced body weight without altering food intake. Furthermore, CN alleviated the accumulation of white adipose tissue and liver mass, along with a reduction in plasma total cholesterol levels. Collectively, these findings suggest that CN enhances the bioavailability of curcumin and exerts potent anti-obesity effects by targeting adipogenesis and lipid metabolism.