Ameliorative effects of glycine in an experimental nonalcoholic steatohepatitis and its correlation between TREM-1 and TREM-2

Inflammation plays an important role in Nonalcoholic Steatohepatitis (NASH), triggering receptor expressed on myeloid cells-1 and 2 (TREM-1 and TREM-2) modulates inflammatory and innate immune, they have been investigated in various inflammatory diseases, but not in NASH. Meanwhile we added glycine in HFO (HFOG) to investigate if the liver pathologic relief is related with TREM-1 and TREM-2. Liver tissue staining and serum indexes showed that the NASH was successful from the 4(th) weekend and glycine can improved many features of NASH. Results from Q-PCR and ELISA study showed that compareaded with control, TREM-1 is upregulated and TREM-2 is downregulated respectively in 4 and 8-week NASH model (TREM-1: p < 0.001; TREM-2: p < 0.001).Compared with HFO group, HFOG group with an extra 5% Glycine into the diet of NASH, we found that all model liver pathologic and serum indexes ameliorated in this group. Furthermore, Results from Q-PCR and ELISA study showed that compareaded with HFO group, TREM-2 of this group is upregulated and TREM-1 is downregulated respectively from the 4(th) weekend, which is more significant at the 8(th) weekend (TREM-1: p <0.001; TREM-2: p =0.048). Pearson correlation showed that TREM-1 and TREM-2 were closely associated with serum ET, TNF-α, TLR-4 and PC III. Besides, using multiple-stepwise regression analysis, we found that the ameliorative effects of glycine in HFOG was mainly related to its counteraction of PC III, TREM-1 and upregulation of TREM-2. Furthermore, we detected the expression of TREM-1 and TREM-2 in gall stone patients without drinking excessively before undergoing cholecystectomy, and found that the rise of TREM-1 and reduction of TREM-2 was close associated with the severity of fatty liver. To conclude, our results support the concept that TREM-1 and TREM-2 were close strongly linked to NASH and NALFD. Glycine can relieve NASH by its anti-fibrosis effect, and this ameliorative effect is related to the expression change of TREM-1/2 to some extent.