SERBEST ve NANOENKAPSÜLE NARİNGENİN FİTOKİMYASAL BİLEŞENİNİN C57BL/6J FARELERDE ADİPOZ DOKUNUN KAHVERENGİLEŞMESİ ÜZERİNE ETKİSİNİN İNCELENMESİ
Özet
Uçar Baş, Kübra., Investigation of the Effect of Free and Nanoencapsulated Naringenin Phytochemical Component on Browning of Adipose Tissue in C57BL/6J Mice, Hacettepe University Graduate School of Health Sciences Nutrition and Dietetics Programme, Doctor of Philosophy Thesis, Ankara, 2024. Naringenin is thought to be a potential therapeutic strategy to combat obesity through the browning of white adipose tissue. The aim of this study was to investigate and compare the effects of naringenin given in nanoencapsulated and free form on body weight and browning of adipose tissue in C57BL/6J mice. In the first phase of the study, naringenin was encapsulated by liposome method and its physical and chemical properties were tested. In the second phase, 48 6-week-old female C57BL/6J mice were divided into 2 main groups: protection (n=24) and recovery (n=24). Each main group was further divided into four subgroups: Nano-naringenin, void, free-naringenin, control. The group that is protective against obesity (protection group) administered high-fat diet and naringenin for 10 weeks. The group that is improve obesity (recovery group) given only high-fat diet for 10 weeks, followed administered by high-fat diet and naringenin for 10 weeks. Naringenin treatments were injected into the tail at a concentration of 20 µM in 100 µl into each mouse 1 time per week. Body weight was measured once a week. Brown adipose tissue, inguinal white adipose tissue and serum samples were collected from each mouse. Browning (UCP-1, PGC1-α, PRDM16, CIDEA) and adipogenesis (PPARγ, C/EBPβ, FABP4) parameters were examined in tissues and serum. The average particle size, polydispersity index, zeta potential, encapsulation efficiency and loading capacity of liposomal naringenin were approximately 215 nm, 0.35, -27 mV, 94.6% and 19.2%, respectively. Liposomal naringenin exhibited sustained and free naringenin exhibited burst release behavior. Liposomal naringenin showed the best physical stability in light and at 4 °C. Free naringenin was found to be more chemically stable in the light and at 4 °C and 22 °C. Free naringenin (3.78±1.20 g and 1.42±0.87 g, respectively) provided less weight gain than liposomal naringenin (7.33±3.56 g and 1.45±1.35 g, respectively) for mice in the protection and recovery groups (p>0.05). In the protection main group, liposomal naringenin increased inguinal white adipose tissue PRDM16 gene expression level 4.29 times more than free naringenin (p=0.010). In the recovery main group, control group increased brown adipose tissue PRDM16 gene expression level 8.29 and 27.62 times more than free and liposomal naringenine, respectively (respectively, p=0.003, p=0.001). Neither formulation caused significant changes in UCP-1, PGC1-α and CIDEA gene expression levels in white and brown adipose tissue. The results demonstrated that free naringenin can be efficiently encapsulated in biocompatible and biodegradable nanoparticles. Future research should focus on studying the effects of liposomal naringenine on adipose tissue.
