Analysis of amino acid profiles of blood over time and biomarkers associatedwith non-alcoholic steatohepatitis in STAM mice

摘要

The changes in free amino acid (AA) levels in blood during the progression fromnon-alcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC) are unclear. Weinvestigated serum AA levels, along with biochemical and histological events, in a mousemodel of NASH. We induced NASH in male C57BL/6J mice with a streptozotocin injection andhigh-fat diet after 4 weeks of age (STAM group). We chronologically (6, 8, 10, 12, and 16weeks, n=4–12 mice/group) evaluated the progression from steatohepatitis to HCC bybiochemical and histological analyses. The serum AA levels were determined using an AAanalyzer. Serum aspartate aminotransferase and alanine aminotransferase levels were higherin the STAM group than in the normal group (non-NASH-induced mice). Histological analysisrevealed that STAM mice had fatty liver, NASH, and fibrosis at 6, 8, and 10 weeks,respectively. Moreover, the mice exhibited fibrosis and HCC at 16 weeks. The serumbranched-chain AA levels were higher in the STAM group than in the normal group,especially at 8 and 10 weeks. The Fischer ratio decreased at 16 weeks in the STAM group,with increasing aromatic AA levels. These results suggested that this model sequentiallydepicts the development of fatty liver, NASH, cirrhosis, HCC, and AA metabolism disorderswithin a short experimental period. Additionally, serum amyloid A was suggested to be auseful inflammation biomarker associated with NASH. We believe that the STAM model will beuseful for studying AA metabolism and/or pharmacological effects in NASH.