Exploring the Potential of Liposomal Delivery of Naringenin and Berberine for Browning Adipose Tissue and Obesity Management

ABSTRACT Naringenin (N) and berberine (B) have been shown to enhance energy expenditure by promoting browning in white adipose tissue (WAT), but their free forms have low stability and bioavailability. This study aimed to develop novel biocompatible and biodegradable liposomes to encapsulate N and B, enhancing their stability and bioavailability. We also investigated the effects of these liposomal formulations compared to their free forms on thermogenesis and browning in 3T3‐L1 preadipocyte cells. The expression of key proteins (uncoupling protein 1 [UCP1], peroxisome proliferator–activated receptor‐gamma coactivator‐1alpha [PGC‐1α], peroxisome proliferator–activated receptor gamma [PPARγ]) and genes related to browning and adipogenesis ( UCP1 , PPARγ , CCAAT/enhancer‐binding protein [ C/EBP ]β, PGC‐1α , cell death–inducing DNA fragmentation factor alpha–like effector A [ CIDEA ], fatty acid–binding protein 4 [ FABP4 ], PR domain containing 16 [ PRDM16 ]) was evaluated following treatment with different dosages of liposomal and free N and B during cell differentiation and maturation. Gene expression was assessed by quantitative real‐time PCR, and protein levels were measured by ELISA, with statistical significance set at p < 0.05. We successfully synthesized biocompatible and biodegradable liposomes. High‐dose liposomal N significantly increased UCP1 gene expression ( p = 0.035), whereas high‐dose liposomal B significantly boosted UCP1 expression ( p = 0.002) and reduced triglyceride levels during differentiation ( p < 0.001). The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay confirmed that all compounds were safe after 24 h, with some adverse effects observed at 48 h. In conclusion, stable liposomes containing N and B were successfully synthesized. Liposomal N increased UCP1 expression, whereas liposomal B not only increased UCP1 expression but also reduced triglyceride levels during differentiation. Further in vitro and in vivo studies are needed to validate these findings and explore their potential in treating obesity. Practical Application : The results of this study highlight the potential use of liposomal delivery systems for naringenin and berberine in obesity management. Liposomal encapsulation enhances the stability, bioavailability, and sustained release of these compounds, making them more effective in promoting the browning of white adipose tissue. This browning process increases energy expenditure and reduces lipid accumulation, which can aid in weight loss and improve metabolic health. Liposomal berberine, in particular, shows significant potential in inducing browning and reducing triglyceride levels during the early stages of adipocyte development. These findings suggest that liposomal naringenin and berberine could be developed into therapeutic interventions for obesity, with further in vivo studies needed to validate these effects. The application of such nanocarrier systems can offer a more targeted and efficient approach to obesity treatment, potentially reducing the dosage and side effects associated with free forms of these compounds.