In the liver tissues of obese diabetic or nondiabetic patients,
triggering receptor expressed on myeloid cells-1 (TREM-1) is usually found to be upregulated, thus leading to upregulation of various inflammatory
cytokines and
lipid accumulation. On the other hand,
nonalcoholic fatty liver disease (
NAFLD), characterized by excess
lipid accumulation, and inflammatory injury in liver, is becoming an epidemic disease, globally. In the present study, we aimed to investigate the
biological role and the underlying mechanisms of TREM-1 in
NAFLD. upregulation of TREM-1 occurred in high-fat diet (HFD)-induced mice
NAFLD model and
oleic acid-treated HepG2 and primary mouse hepatocytes cell model at
messenger RNA and
protein levels. Functional studies established that overexpression of TREM-1 displayed
hyperlipidemia, and increased in inflammatory indicators and
lipid accumulation-related genes, which was ameliorated by knockdown of TREM-1. Our results also showed that obvious
lipid accumulation and inflammatory injury occurred in the liver tissue of HFD-fed mice, while treatment with lentiviral vector short hairpin TREM showed marked improvement in tissue morphology and architecture and less
lipid accumulation, thus deciphering the mechanism through which knockdown of TREM-1 ameliorated the inflammatory response and
lipid accumulation of
NAFLD mice through inactivation of the nuclear factor-κB (NF-κB) and PI3K/AKT signal pathways, respectively. In conclusion, TREM-1/NF-κB and TREM-1/PI3K/AKT axis could be an important mechanism in ameliorating the inflammatory response and
lipid accumulation, respectively, thus shedding light on the development of novel
therapeutics to the treatment of
NAFLD.