Comparison of free <i>vs.</i> liposomal naringenin in white adipose tissue browning in C57BL/6j mice

Naringenin may play a role in browning by increasing thermogenic gene expression. In this study, we encapsulated naringenin using a liposomal formulation and examined the effects of both free and liposomal naringenin on white adipose tissue browning in C57BL6/J mice. In the first phase of the study, naringenin was encapsulated by the liposome method, which is biocompatible and biodegradable. The physical and chemical properties of liposomal naringenin were tested. In the second phase, a total of 48 six-week-old mice were divided into two main groups: prevention and recovery. Each main group was divided into four subgroups: nano-naringenin, void, free-naringenin, and control. The prevention group received a high-fat diet for 10 weeks along with weekly intravenous injections of 20 µM naringenin. On the other hand, the recovery group was first subjected to a high-fat diet for 10 weeks, followed by an additional 10 weeks of the same diet, along with weekly intravenous injections of 20 µM naringenin. Body weight was measured once per week, and brown adipose tissue, inguinal white adipose tissue, and serum samples were collected from each mouse. The mean particle size, polydispersity index and zeta potential values of liposomal naringenin were ∼207 nm, 0.35, and -27 mV, respectively. The encapsulation and loading efficiencies of liposomal naringenin were 94.6 and 19.2%, respectively. Liposomal naringenin exhibited sustained-release behavior, while free naringenin showed a burst-release profile. Liposomal naringenin showed the best physical stability in light and at 4 °C, while free naringenin was more chemically stable in light and at 4 and 22 °C. Free and liposomal naringenin did not significantly reduce weight gain. In the prevention group, liposomal naringenin increased PRDM16 gene expression in inguinal white adipose tissue 4.29 times more than free naringenin (<i>p</i> = 0.010). However, neither formulation significantly altered the expression levels of other browning or adipogenesis markers in the tissues. The results suggest that free naringenin can be efficiently encapsulated in biocompatible and biodegradable nanoparticles. Further research is needed to better understand the physiological effects of liposomal naringenin.