Bi-directional regulation between adiponectin and plasminogen activator-inhibitor-1 in 3T3-L1 cells

Adiponectin (APN) and plasminogen activator inhibitor-1 (Pai-1) are adipocytokines, and low levels of serum APN and high levels of PAI-1 are observed in obese patients. Moreover, both APN and Pai-1 are known to be involved in colorectal carcinogenesis. Recently, we demonstrated that serum Pai-1 levels are elevated in APN-deficient mice. We hypothesized that Pai-1 expression levels could be depressed by APN. Thus, we aimed to clarify the bi-directional regulatory mechanisms between APN and Pai-1.

We investigated the expression levels of APN and Pai-1 during 3T3-L1 pre-adipocyte differentiation, and examined the role of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)-γ on APN and Pai-1 expression at early and late differentiation stages.

In the early phase of differentiation, Pai-1 expression increased and APN slightly decreased. Reduction of Pai-1 or activation of PPARγ resulted in elevation of APN, and supplementation of APN with activation of AMPK resulted in reduction of Pai-1. In the late phase of differentiation, APN increased its expression and Pai-1 decreased. Supplementation of Pai-1 resulted in a slight reduction of APN.

It is suggested that APN and Pai-1 expressions are inversely-regulated. Understanding of the regulatory system between APN and Pai-1 may lead to finding novel methods for colorectal cancer prevention.