Effects and mechanism of TREM-1 on inflammatory response and lipid metabolism in mice with nonalcoholic fatty liver disease

Abstract

Objective Analysis of the effect of triggering receptor-1 expressed on myeloid cells (TREM-1) in nonalcoholic fatty liver disease (NAFLD) and the mechanism. Methods The oleic acid-treated HepG2 cells were divided into model group, overexpression group, interference group A, interference group B and negative control group. The mouse model of NAFLD was generated and randomly divided into (nuclear factor-κB) NF-κB inhibition group, protein kinase B (AKT) inhibition group, knockout group A, knockout group B and control group. The expression of inflammatory factors and TREM-1 in liver tissue was detected by PCR, and fat accumulation was detected by oil red O staining. Western blotting was used to detect the expression of TREM-1 and signaling pathway proteins, and HE staining was used to detect liver tissue changes. Results TREM-1 was up-regulated in liver tissue of NAFLD mice [(0.936±0.127) vs. (0.432±0.105)] and in oleic acid-treated HepG2 cells. In oleic acid-treated HepG2 cells, overexpression of TREM-1 increased inflammatory factor expression and increased lipid droplets; inhibition of TREM-1 expression decreased inflammatory factor expression, and lipid droplets decreased. Knockout of TREM-1 and inhibition of NF-κB in NAFLD mice reduced hepatocyte inflammatory factor expression and reduced liver damage; knockout of TREM-1 and inhibition of AKT reduced liver tissue lipids and drops accumulate. Conclusions The overexpression of TREM-1 in NAFLD mice liver tissue can regulate inflammatory factor expression and lipid droplets through NF-κB and AKT signal pathway. TREM-1 might be a potential therapeutic target of NAFLD. Key words: Inflammation; Nonalcoholic fatty liver disease; Triggering receptor-1 expressed on myeloid cells; Lipid accumulation