Magnolol promotes thermogenesis and attenuates oxidative stress in 3T3-L1 adipocytes.

OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively. Induction of thermogenesis and suppression of oxidative stress in 3T3-L1 adipocytes were further validated by immunofluorescence. RESULTS: Magnolol significantly enhanced expression of a core set of brown fat-specific marker genes (Ucp1, Cd137, Prdm16, Cidea, and Tbx1) and proteins (UCP1, PRDM16, and PGC-1α). Increased expression of UCP1 and other brown fat-specific markers contributed to the browning of 3T3-L1 adipocytes possibly via activation of the AMPK, PPARγ, and protein kinase A (PKA) pathways. In addition, magnolol up-regulated key fatty acid oxidation and lipolytic markers (CPT1, ACSL1, SIRT1, and PLIN) and down-regulated lipogenic markers (FAS and SREBP1). Magnolol also reduced the production and release of reactive oxygen species. CONCLUSION: The current data suggest possible roles for magnolol in browning of white adipocytes, augmentation of lipolysis, and thermogenesis, as well as repression of oxidative stress and lipogenesis. Thus, magnolol may be explored as a potentially promising therapeutic agent for the prevention of obesity and other metabolic disorders.

Nobiletin induces brown adipocyte-like phenotype and ameliorates stress in 3T3-L1 adipocytes.

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/EBPß, 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.