Leucine-rich glioma inactivated 3 and tumor necrosis factor-α regulate mutually through NF-κB

Abstract

Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI family. We previously reported that LGI3 increased in obese adipose tissues and suppressed adipogenesis through its receptor, ADAM23. We proposed that LGI3 may be a pro-inflammatory adipokine secreted predominantly by preadipocytes and macrophages. In this study, we showed that LGI3 and tumor necrosis factor-alpha (TNF-alpha) upregulated each other in 3T3-L1 cells. Treatment of 3T3-L1 preadipocytes with LGI3 protein increased TNF-alpha mRNA and protein. LGI3 treatment led to NF-kappa B activation and binding to an NF-kappa B binding site (-523 to -514) in TNF-alpha promoter. TNF-alpha treatment increased mRNA and protein expression of LGI3 and ADAM23. TNF-alpha increased NF-kappa B binding to a predicted binding site (-40 to -31) in LGI3 promoter. High fat diet-fed mice showed that LGI3 and TNF-alpha were increased and colocalized in adipose tissue inflammation. Taken together, these results suggested that mutual upregulation of LGI3 and TNF-alpha may play a role in adipose tissue inflammation in obesity. (C) 2015 Elsevier Ltd. All rights reserved.