Genistein and daidzein, typical soy isoflavones, inhibit TNF‐α‐mediated downregulation of adiponectin expression via different mechanisms in 3T3‐L1 adipocytes

Scope Previous reports suggest that soy isoflavones have multiple biological functions and may help to restore adiponectin expression and insulin sensitivity. However, little is known about whether soy isoflavones can inhibit the downregulation of adiponectin and their molecular mechanisms. In the present study, we demonstrate that genistein (Gen) or daidzein (Dai) can significantly inhibit the downregulation of adiponectin expression via unique and different molecular mechanisms. Methods and results Pretreatment with Gen or Dai significantly inhibited the tumor necrosis factor-alpha (TNF-α)-mediated downregulation of adiponectin expression in 3T3-L1 adipocytes. Gen inhibited the TNF-α-induced c-Jun-NH2-terminal kinase (JNK) signaling that is involved in adiponectin expression. Molecular docking studies based on JNK1 with Gen or Dai clearly supported our experimental results. However, Dai did not significantly inhibit JNK signaling. Dai did, however, inhibit the TNF-α-induced downregulation of forkhead box-containg protein O1, which is also involved in adiponectin expression. Conclusion These data demonstrate that: (i) both Gen and Dai significantly inhibit the TNF-α-mediated downregulation of adiponectin in adipocytes; (ii) Gen is an effective inhibitor of JNK activation, thus inhibiting the TNF-α-mediated downregulation of adiponectin; and (iii) Dai can inhibit the downregulation of adiponectin by restoring the TNF-α-mediated reduction of forkhead box-containg protein O1 protein expression.