TY - JOUR AB - In the present study, we evaluated the protective effects of amentoflavone (AMF) against high-fat (HF) diet-induced metabolic dysfunction and focused on the influence of AMF on adipogenic differentiation during 3T3-L1 adipocyte differentiation. For this purpose, male Wistar rats were fed a HF diet or a HF diet with AMF (10 or 50 mg/kg). We found that AMF protected against HF diet-induced metabolic dysfunction in a dose-dependent manner, as evidenced by a decrease in the fasting blood glucose levels, fasting insulin levels and the homeostatic model assessment-insulin resistance index (HOMA‑IR), as well as by a decrease in the glucose level, as shown by the intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test. Moreover, the results revealed that AMF significantly inhibited the increase in body weight, the weight of perirenal adipose tissues and the serum triglyceride (TG) content of the rats fed the HF diet in a dose-dependent manner. AMF also inhibited the accumulation of oil droplets in differentiated 3T3-L1 adipocytes in a concentration-dependent manner. The incubation of the cells with AMF for 0-8, 0-2, 2-4, or 4-8 days markedly inhibited adipogenesis. During the early phase of the adipocyte differentiation of 3T3-L1 cells, AMF decreased CCAAT/enhancer-binding protein (C/EBP) β expression in a concentration-dependent manner, leading to the inhibition of mitotic clonal expansion (MCE). Moreover, our results demonstrated that AMF significantly increased reactive oxygen species (ROS) generation in the cells and the antioxidant, N-acetylcysteine (NAC), markedly attenuated the inhibitory effects of AMF on adipogenesis. AMF also inhibited the expression of peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα and the expression of downstream targets in a concentration-dependent manner. The overexpression of PPARγ and C/EBPα  (by transfection with respective overexpression plasmids) attentuated the inhibitory effects of AMF on the formation of oil droplets. The inhibitory effects of AMF on adipocyte differentiation may contribute to its protective effects against HF diet-induced metabolic dysfunction. Overall, the data in our study provide novel insight into the mechanisms responsible for the protective effects of AMF against HF diet-induced metabolic dysfunction and those for its inhibitory effect on adipocyte differentiation. AD - Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China Department of Endocrinology, Xi'an No. 1 Hospital, Xi'an, Shaanxi 710002, P.R. China Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China AU - Chen,Guangyong AU - Han,Yangdong AU - He,Wang AU - Liang,Feng DA - 2016/12/01 DO - 10.3892/ijmm.2016.2772 EP - 1767 IS - 6 JO - Int J Mol Med KW - amentoflavone metabolic dysfunction adipocyte differentiation CCAAT/enhancer-binding protein peroxisome proliferator-activated receptor γ PY - 2016 SN - 1107-3756 1791-244X SP - 1759 ST - Amentoflavone protects against high fat-induced metabolic dysfunction: Possible role of the regulation of adipogenic differentiation T2 - International Journal of Molecular Medicine TI - Amentoflavone protects against high fat-induced metabolic dysfunction: Possible role of the regulation of adipogenic differentiation UR - https://doi.org/10.3892/ijmm.2016.2772 VL - 38 ER -