Leucine-rich glioma inactivated 3 associates negatively with adiponectin.

Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI/epitempin family. We previously reported that LGI3 was expressed in adipose tissues and suppressed adipogenesis through its receptor, ADAM23. We proposed that LGI3 may be a candidate adipokine with pro-inflammatory activity. To investigate the role of LGI3 in adipose tissues, we analyzed cytokine profile in LGI3 knockout mice. Protein array analysis showed that adiponectin was significantly increased in adipose tissues and plasma of LGI3 knockout mice. SiRNA-mediated knockdown of LGI3 increased adiponectin in 3T3-L1 preadipocytes. Treatment of differentiating 3T3-L1 cells with LGI3 protein decreased adiponectin in a dose-dependent manner. High fat diet (HFD)-fed mice showed expression of LGI3 in adipose tissue macrophages in addition to adipocytes that expressed LGI3 in both normal chow-fed and HFD-fed mice. The 60-kDa LGI3 was selectively increased in adipose tissues of HFD mice in which adiponectin was downregulated. Taken together, these results suggested that LGI3 may participate in adipose tissue homeostasis by negatively regulating adiponectin.