TAF treatment ameliorates liver injury in the NASH mouse model
We established a NASH mouse model using STZ and HFHC diets to evaluate the effects of TAF on NASH (Fig 1A). Liver function tests were performed by measuring the serum ALT, AST, and triglyceride (TRIG) levels to confirm the NASH model and TAF effects. ALT, AST, and TRIG levels were lower in the TAF-treated HFHC diet-fed group than in the mock-treated ones (Fig 1B). Body weight and random glucose levels were measured for 2 weeks. The total liver weight of the TAF-treated HFHC diet-fed mice was lower than that of the mock-treated ones. (Supplementary Fig S1A). Haematoxylin and eosin (H&E) staining of paraffin-embedded liver sections showed that hepatocyte necrosis and sinusoidal congestion were significantly reduced in the livers of the TAF-treated HFHC diet-fed group than in those of the mock-treated ones. Sirius red staining showed that the collagen deposition area was decreased in the livers of the TAF-treated HFHC diet-fed group compared to those of the mock-treated one. Moreover, the IHC results showed that the percentages of LPS- and toll-like receptor 4 (TLR4)-positive cells were higher in the mock-treated HFHC diet group than in the TAF-treated group (Fig 1C). The TLR4- or LPS-positive cell frequency was lower in the TAF-treated HFHC diet group than in the mock-treated one. The area ratio of stained collagen was lower in the TAF-treated HFHC diet group than in the mock-treated one. NASH Activity Score (NAS) was decreased in the livers of the TAF-treated HFHC diet-fed group compared to those of the mock-treated one (Fig 1D).
We established a NASH mouse model using a choline-deficient, L-amino acid-defined, high-fat (CDAHF) diet to evaluate TAF’s role in NASH. (Fig 1E). ALT, AST, and TRIG levels were lower in the TAF-treated CDAHF diet-fed group than in the mock-treated one (Fig 1F). Body weight and random glucose levels were measured for 2 weeks. The total liver weight of the TAF-treated CDAHF diet-fed group was lower than that of the mock-treated one (Supplementary Fig S1B). H&E staining of paraffin-embedded liver sections showed that hepatocyte necrosis and sinusoidal congestion were significantly reduced in the TAF-treated CDAHF diet-fed group’s livers compared to those of the mock-treated one (Supplementary Fig S1C).