Serbest ve Nanoenkapsüle Berberin Fitokimyasal Bileşeninin C57bl/6j Farelerde Adipoz Dokunun Kahverengileşmesi Üzerine Etkisinin İncelenmesi

Abstract

Berberine increases adipose tissue browning and is considered a potential bioactive compound in the fight against obesity. The aim of this study is to examine the effects of intravenously administered nanoencapsulated and free berberine phytochemicals on body weight, activation of brown adipose tissue, and browning of white adipose tissue in female C57BL/6J mice. The study was conducted in three phases. In the first phase, a liposomal nanoencapsulation method was developed and tested. In the second phase, 48 six-week-old C57BL/6J female mice were divided into prevention (n=24) and recovery (n=24) groups after 1 week of stabilization. The prevention group received a high-fat diet and treatment injections for 10 weeks, while the recovery group was given a high-fat diet for 10 weeks, followed by 10 weeks of treatment injections along with the diet. The treatment groups were free berberine (10 µM), nano-berberine (10 µM), void, and control. The treatments were freshly prepared every week and administered by tail vein injection (100 µL). Body weight was measured weekly. In the third phase of the study, adipogenesis (PPARγ, C/EBPβ, FABP4) and browning (UCP1, PGC1α, PRDM16, CIDEA) markers were analyzed in collected serum and tissues. Nano-berberine had a particle size of 215 nm, zeta potential of -27 mV, and a polydispersity index of 0.3. Encapsulation efficiency was 96.0% and loading capacity was 21.1%. Free berberine exhibited burst release, while nano-berberine showed sustained release. Nano-berine was more stable at 4°C in light, while free berberine was more stable at 4°C or 37°C in light. In the recovery group, the group that gained the least weight was the nano-berberine-treated group, while the free berberine group lost weight. In the prevention group, nano-berberine-treated mice had higher PPARγ expression in inguinal white adipose tissue compared to the free berberine and control groups (p=0.024, p=0.005). Free berberine-treated mice had higher PPARγ expression in brown adipose tissue compared to the control group (p=0.029). In the prevention group, the expression of PRDM16 and CIDEA in inguinal white adipose tissue was higher in the nano-berberine-treated groups compared to the other groups (p<0.05). In the brown adipose tissue of nano-berberine-treated mice, CIDEA expression was higher compared to the free berberine and void groups (p=0.017, p=0.021). In conclusion, a more stable and bioavailable nano-berberine was synthesized. The berberine dose (10 µM) may not have been sufficient to induce significant changes in adipogenesis and browning markers. Further preclinical studies with higher doses and extended durations are required.