Activity transcription factor 3 suppressed LPS‐induced adipocyte inflammation in experimental sepsis

Abstract

Endotoxemia, a state of excessive endotoxin (lipopolysaccharide, LPS) in the circulation, frequently results in fatal sepsis. Activating transcription factor (ATF)‐3 is a member of the ATF/cAMP‐response element‐binding protein family of transcriptional factors. It is also induced by stress condition in a variety of tissues, including the adipose tissue. The aim of this study is to assess the possible protective role of ATF3 in adipose tissue inflammation of LPS‐induced polymorphonuclear leukocyte recruitment in experimental sepsis. ATF3‐knockout (KO) and wild‐type mice (WT) were injected with LPS (5 mg/kg, ip) to induce endotoxemia. Multifaceted approaches including the in vivo animal endotoxemic mice model for examining biochemical analysis, the expression of inflammatory mediators, and pathophysiological examinmation in the adipocytes were investigated. Results demonstrated that LPS enhanced ATF3 protein expression in WT control mice, but not in ATF3‐KO group in the adipocytes. We found that the protein expression of iNOS and the numbers of polymorphonuclear leukocyte were significantly increased in the adipose tissue of KO mice, but not observed in WT mice after LPS induction. Furthermore, restored ATF3 gene expression by transfection of adeno‐associated virus (AAV) in the KO mice, the increased WBC levels, iNOS expression, and LPS‐mediated polymorphonuclear leukocyte recruitment were significantliy suppressed that comparing to the WT mice. These results suggested that ATF3 gene may play a critical role to overcome the adipose tissue inflammation in experimental sepsis.Support or Funding Informationsupported by MOST and Tzu Chi Medical center