Browning of white adipocytes (beiging) is an attractive therapeutic strategy against obesity and its associated metabolic complications. Nobiletin (NOB) is a polymethoxylated flavone present in citrus fruits and has been reported to have anti-obesity effects. Here, we report that nobiletin exerts dual modulatory effects on adipocytes via induction of browning in 3T3-L1 white adipocytes and amelioration of stress in adipocytes. Nobiletin-induced beiging was investigated by determining expression levels of beige-specific genes and proteins by RT-PCR and immunoblot analysis, respectively. Nobiletin treatment rapidly elevated the expression levels of beige-specific genes such as Cd137, Cidea, Tbx1, and Tmem26. Further, nobiletin enhanced expression of the key transcription factors C/EBPβ, PPARδ, and PPARα, which are responsible for remodeling of white adipocytes. Nobiletin also strikingly activated HIB1B brown adipocytes and induced mitochondrial biogenesis in 3T3-L1 white adipocytes. In addition, nobiletin altered the expression of several lipid metabolism-related proteins such as ACOX1, CPT1, FAS, p-PLIN, SREBP and SIRT1. Moreover, nobiletin ameliorated stress in adipocytes by inhibiting expression levels of key stress molecules such as JNK and c-JUN. Nobiletin-induced browning could be mediated by tight regulation of kinases, as nobiletin induced PKA and p-AMPK at the protein expression level, and inhibition of PKA and p-AMPK by H-89 and dorsomorphin, respectively, abolished expression of the thermogenic markers PGC-1α and UCP1. Taken together, our findings suggest that nobiletin plays a modulatory role in adipocytes via induction of browning in 3T3-L1 white adipocytes and activation of HIB1B brown adipocytes combined with amelioration of stress in adipocytes, thereby exhibiting therapeutic potential against obesity.

白色脂肪细胞褐变（米色）是一种针对肥胖及其相关代谢并发症的有吸引力的治疗策略。Nobiletin（NOB）是存在于柑橘类水果中的一种聚甲氧基黄酮，据报道具有抗肥胖作用。在这里，我们报告诺比列汀通过诱导3T3-L1白色脂肪细胞中的褐变和减轻脂肪细胞中的压力，对脂肪细胞发挥双重调节作用。通过分别通过RT-PCR和免疫印迹分析确定米色特异性基因和蛋白质的表达水平，研究了Nobiletin诱导的拟南芥。Nobiletin治疗可迅速提高米色特异性基因（如Cd137，Cidea，Tbx1和Tmem26）的表达水平。此外，诺比列汀增强了负责白色脂肪细胞重塑的关键转录因子C /EBPβ，PPARδ和PPARα的表达。诺比列汀还惊人地激活了HIB1B棕色脂肪细胞，并诱导了3T3-L1白色脂肪细胞中的线粒体生物发生。此外，nobiletin改变了几种脂质代谢相关蛋白的表达，例如ACOX1，CPT1，FAS，p-PLIN，SREBP和SIRT1。此外，诺比列汀通过抑制关键应激分子（如JNK和c-JUN）的表达水平来减轻脂肪细胞的应激。Nobiletin诱导的褐变可以通过严格调节激酶来介导，因为Nobiletin在蛋白质表达水平上诱导PKA和p-AMPK，并且分别由H-89和dorsomorphin抑制PKA和p-AMPK从而废除了产热标记物的表达。 PGC-1α和UCP1。在一起