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

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  • Iida Ayaka
    School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, 1-10-1 Heisei-cho, Yokosuka, Kanagawa 238-8522, Japan Graduate School of Health and Environmental Sciences, Fukuoka Women’s University, 1-1-1 Kasumigaoka, Higashi-ku, Fukuoka 813-8529, Japan
  • Kuranuki Sachi
    School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, 1-10-1 Heisei-cho, Yokosuka, Kanagawa 238-8522, Japan
  • Yamamoto Ryoko
    Department of Applied Biology and Food Sciences, Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki, Aomori 036-8560, Japan
  • Uchida Masaya
    Department of Creative Engineering, National Institute of Technology, Ariake College, 150 Higashi hagio-machi, Omuta, Fukuoka 836-8585, Japan
  • Ohta Masanori
    Graduate School of Health and Environmental Sciences, Fukuoka Women’s University, 1-1-1 Kasumigaoka, Higashi-ku, Fukuoka 813-8529, Japan
  • Ichimura Mayuko
    Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
  • Tsuneyama Koichi
    Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
  • Masaki Takayuki
    Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
  • Seike Masataka
    Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
  • Nakamura Tsuyoshi
    Graduate School of Health and Environmental Sciences, Fukuoka Women’s University, 1-1-1 Kasumigaoka, Higashi-ku, Fukuoka 813-8529, Japan

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<p>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.</p>

収録刊行物

  • Experimental Animals

    Experimental Animals 68 (4), 417-428, 2019

    公益社団法人 日本実験動物学会

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