Piceatannol, a natural
stilbene, is an analog and a metabolite of
resveratrol. Despite a well documented health benefit of
resveratrol in intervention of the development of
obesity, the role of
piceatannol in the development of adipose tissue and related diseases is unknown. Here, we sought to determine the function of
piceatannol in adipogenesis and elucidate the underlying mechanism. We show that
piceatannol inhibits adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner at noncytotoxic concentrations. This anti-adipogenic property of
piceatannol was largely limited to the early event of adipogenesis. In the early phase of adipogenesis,
piceatannol-treated preadipocytes displayed a delayed cell cycle entry into G(2)/M phase at 24 h after initiation of adipogenesis. Furthermore, the
piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the
insulin-signaling pathway.
Piceatannol dose-dependently inhibited differentiation mixture-induced phosphorylation of
insulin receptor (IR)/
insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis. Moreover, we showed that
piceatannol is an inhibitor of IR
kinase activity and
phosphatidylinositol 3-kinase (PI3K). Our kinetics study of IR further identified a K(m) value for
ATP of 57.8 μm and a K(i) value for
piceatannol of 28.9 μm. We also showed that
piceatannol directly binds to IR and inhibits IR
kinase activity in a mixed noncompetitive manner to
ATP, through which
piceatannol appears to inhibit adipogenesis. Taken together, our study reveals an anti-adipogenic function of
piceatannol and highlights IR and its downstream
insulin signaling as novel targets for
piceatannol in the early phase of adipogenesis.