Resveratrol inhibits 3T3‐L1 adipogenesis through direct regulation of insulin receptor

Adipogenesis which is the process of mature adipocyte formation from precursor cells has been suggested as a target mechanism to regulate obesity. Resveratrol is a natural bioactive compound with anti‐inflammatory and anti‐cancer properties. Although resveratrol was recently found to inhibit adipogenesis, the molecular basis underlying resveratrol's function in adipogenesis is unclear. Here we demonstrate that resveratrol significantly inhibited adipogenesis in a dose‐dependent manner and this inhibition was not due to cytotoxic effect of resveratrol. This result was further supported by the evidence of decreased mRNA expression level of adipogenic transcription factors, including peroxisome proliferator‐activated receptor γ, CCAAT/enhancer binding protein (C/EBP)α, and C/EBPβ, in resveratrol‐treated cells. The inhibitory effect of resveratrol on adipogenesis is greatly attributable to the inhibition of the early stage (i.e., Day 0–2) of adipogenesis. During the early stage of adipogenesis, resveratrol arrested cell cycle progression, and suppressed insulin signaling pathway upregulated by adipogenic stimuli as evidenced by suppression of insulin‐induced phosphorylation of Akt, insulin receptor substrate‐1, and insulin receptor (IR). Moreover, we observed that resveratrol directly inhibited the kinase activity of IR. Taken together, our results elucidate an anti‐adipogenic function of resveratrol and reveal insulin signaling pathway as a novel target for resveratrol in suppressing adipogenesis. Grant Funding Source : Purdue Research Foundation