β-Carotene-loaded cationic nanoparticles ameliorate MASLD via modulating lipid homeostasis and gut microbiome

Metabolic dysfunction-associated steatotic liver disease (MASLD) is, increasingly, a major threat to human health, yet without any approved drug. β-carotene (BC) contributes to alleviating several metabolic diseases. However, the bioavailability of BC is hindered by hydrophobicity and environmental sensitivity. Herein, we explore the utilization of cationic lipid-assisted nanoparticles to achieve efficient delivery of BC. In the MASLD model, NP-BC ameliorated the development of metabolic disorders, insulin resistance, inflammatory injury and hepatic steatosis. Transcriptomic analysis showed that NP-BA rectifies various pathways involved in steatosis development by inhibiting the PI3K/AKT/mTOR pathway and PPARγ gene expression. Meanwhile, NP-BC also reshaped the composition of gut microbiota in MASLD mice by reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of beneficial bacteria. Taken together, our study demonstrates that NP-BC can improve MASLD and may be a promising candidate for treating MASLD.