EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, 2025 (SCI-Expanded, Scopus)
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-1 alpha], peroxisome proliferator-activated receptor gamma [PPAR gamma]) and genes related to browning and adipogenesis (UCP1, PPAR gamma, CCAAT/enhancer-binding protein [C/EBP]beta, PGC-1 alpha, 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.