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Exp Anim. 2019 Jun 1. doi: 10.1538/expanim.18-0152. [Epub ahead of print]

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

Author information

1
School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services.
2
Graduate School of Health and Environmental Sciences, Fukuoka Women's University.
3
Department of Applied Biology and Food Sciences, Faculty of Agriculture and Life Science, Hirosaki University.
4
Department of Creative Engineering, National Institute of Technology, Ariake College.
5
Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School.
6
Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University.
7
Department of Gastroenterology, Faculty of Medicine, Oita University.

Abstract

The changes in free amino acid (AA) levels in blood during the progression from non-alcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC) are unclear. We investigated serum AA levels, along with biochemical and histological events, in a mouse model of NASH. We induced NASH in male C57BL/6J mice with a streptozotocin injection and high-fat diet after 4 weeks of age (STAM group). We chronologically (6, 8, 10, 12, and 16 weeks, n=4-12 mice/group) evaluated the progression from steatohepatitis to HCC by biochemical and histological analyses. The serum AA levels were determined using an AA analyzer. Serum aspartate aminotransferase and alanine aminotransferase levels were higher in the STAM group than in the normal group (non-NASH-induced mice). Histological analysis revealed 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 serum branched-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 sequentially depicts the development of fatty liver, NASH, cirrhosis, HCC, and AA metabolism disorders within a short experimental period. Additionally, serum amyloid A was suggested to be a useful inflammation biomarker associated with NASH. We believe that the STAM model will be useful for studying AA metabolism and/or pharmacological effects in NASH.

KEYWORDS:

amino acid metabolism disorder; diabetes; hyperlipidemia; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis

PMID:
31155606
DOI:
10.1538/expanim.18-0152
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