Inhibitory effect 6-gingerol on adipogenesis through activation of the Wnt/β-catenin signaling pathway in 3T3-L1 adipocytes

• 6-gingerol inhibits adipogenic differentiation and lipid accumulation.
• 6-gingerol activates the Wnt/β-catenin signaling pathway during adipogenic differentiation.
• β-catenin plays a critical role in adipogenic differentiation.

6-Gingerol has been reported to inhibit adipogenesis and lipid content accumulation. However, the mechanism of its anti-adipogenic effect remains unclear. Our aim is to investigate the molecular mechanism of the anti-adipogenic effect of 6-gingerol. The lipid content in adipocytes was measured by Oil Red O staining and cell viability was analyzed by MTT assay. The extent of suppression of differentiation by 6-gingerol was characterized by measuring the triglyceride content and GPDH activity. The regulation of adipogenic markers and the components of the Wnt/β-catenin pathway were analyzed by real-time PCR and Western blotting. The nuclear location of β-catenin was identified using immunofluorescence assay. Small interfering RNA transfection was conducted to elucidate the crucial role of β-catenin in anti-adipogenic effect of 6-gingerol. Our results showed that 6-gingerol inhibited the adipogenesis and lowered the mRNA expression levels of transcription factors and the key lipogenic enzymes in 3T3-L1 cells. The effect of 6-gingerol on adipogenic differentiation was accompanied by stimulating the activation of the Wnt/β-catenin signaling. In addition, we found that 6-gingerol induced phosphorylations of glycogen synthase kinase-3β(GSK-3β), and promoted the nuclear accumulation of β-catenin. Importantly, the inhibitory effect of 6-gingerol on adipogenic differentiation was reversed after the siRNA knockdown of β-catenin was added. Our findings demonstrated that 6-gingerol inhibits the adipogenic differentiation of 3T3-L1 cells through activating the Wnt/β-catenin signaling pathway.

Mechanism of 6-gingerol-induced inhibition of adipogenesis differentiation. 6-gingerol induces the activation of the Wnt/β-catenin pathway leading to the up-regulation of β-catenin which inhibits the expression of PPAR-γ and C/EBP-α.Figure optionsDownload as PowerPoint slide