抄録
BDNF (brain derived neurotrophic factor) is known as a critical player of neural development, synaptic plasticity and a putative rescue factor for neuronal disorders. Recent studies suggest that BDNF also has potential regulatory roles in peripheral tissues. We found that BDNF and TrkB-T1, the truncated form of high affinity BDNF receptor TrkB, expressed in matured adipocytes. Moreover BDNF dramatically increased the expression in white adipose tissue (WAT) in obese mouse. Here we report the novel regulatory role of BDNF in adipokine expression in adipocytes. BDNF suppressed mRNA expression of atherosclerogenic adipokine PAI-1 (plasminogen activator inhibitor-1) in matured adipocytes, both of WAT in vivo and 3T3-L1 adipocytes in vitro. Our data revealed that dephosphorylated form of FoxO1 existed in the nucleus and promoted PAI-1 mRNA expression by binding to the FRE/IRE sequence in the promoter and enhancer region. In contrast, BDNF increased the phosphorylation of FoxO1 in PI3-K/Akt and MEK/ERK1/2/S6K dependent pathways and translocated it from the nucleus to cytoplasm, then suppressing PAI-1 mRNA expression. Akt activated by PI3-K phosphorylated Thr24 and Ser256 of FoxO1, and S6K activated by MEK/ERK1/2 phosphorylated the Ser256. siRNA for TrkB inhibited Akt and ERK1/2 phosphorylation in 3T3-L1 adipocytes in response to BDNF. These results suggest that BDNF/TrkB-T1 plays an important role in PAI-1 expression in adipocytes. This pathway may be a target for the therapy of metabolic syndrome. [J Physiol Sci. 2008;58 Suppl:S138]
