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Sci Rep

Title:		Non-target GC-MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice
Author(s):		Kato M; Yamaguchi M; Ooka A; Takahashi R; Suzuki T; Onoda K; Yoshikawa Y; Tsunematsu Y; Sato M; Yoshioka Y; Igarashi M; Hayakawa S; Shoji K; Shoji Y; Ishikawa T; Watanabe K; Miyoshi N;
Address:		"Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka, 422-8526, Japan. Department of Food Science and Nutrition, Faculty of Human Life and Science, Doshisha Women's College of Liberal Arts, Kyoto, Japan. School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo, Japan. Advanced Clinical Research Center, Institute of Neurological Disorders, Kawasaki, Kanagawa, Japan. Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. Basic Nutrition, Kagawa Nutrition University, Saitama, Japan. Department of Food Science and Nutrition, Shizuoka Eiwa Gakuin University Junior College, Shizuoka, Japan. Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka, 422-8526, Japan. miyoshin@u-shizuoka-ken.ac.jp"
Journal Title:		Sci Rep
Year:		2023
Volume:		20230601
Issue:		1
Page Number:		8924 -
DOI:		10.1038/s41598-023-36091-7
ISSN/ISBN:		2045-2322 (Electronic) 2045-2322 (Linking)
Abstract:		"The increased incidence of obesity in the global population has increased the risk of several chronic inflammation-related diseases, including non-alcoholic steatohepatitis (NASH)-hepatocellular carcinoma (HCC). The progression from NASH to HCC involves a virus-independent liver carcinogenic mechanism; however, we currently lack effective treatment and prevention strategies. Several reports have suggested that fecal volatile organic compounds (VOCs) are strongly associated with NASH-HCC; therefore, we explored the biomarkers involved in its pathogenesis and progression. Fecal samples collected from control and NASH-HCC model STAM mice were subjected to headspace autosampler gas chromatography-electron ionization-mass spectrometry. Non-target profiling analysis identified diacetyl (2,3-butandione) as a fecal VOC that characterizes STAM mice. Although fecal diacetyl levels were correlated with the HCC in STAM mice, diacetyl is known as a cytotoxic/tissue-damaging compound rather than genotoxic or mutagenic; therefore, we examined the effect of bioactivity associated with NASH progression. We observed that diacetyl induced several pro-inflammatory molecules, including tumor necrosis factor-alpha, cyclooxygenase-2, monocyte chemoattractant protein-1, and transforming growth factor-beta, in mouse macrophage RAW264.7 and Kupffer KPU5 cells. Additionally, we observed that diacetyl induced alpha-smooth muscle actin, one of the hallmarks of fibrosis, in an ex vivo cultured hepatic section, but not in in vitro hepatic stellate TWNT-1 cells. These results suggest that diacetyl would be a potential biomarker of fecal VOC in STAM mice, and its ability to trigger the macrophage-derived inflammation and fibrosis may partly contribute to NASH-HCC carcinogenesis"
Keywords:		"Mice Animals *Non-alcoholic Fatty Liver Disease/pathology *Carcinoma, Hepatocellular/pathology *Volatile Organic Compounds/pharmacology *Liver Neoplasms/etiology Gas Chromatography-Mass Spectrometry Diacetyl Liver/pathology Carcinogenesis/pathology Biomar;"
Notes:		"MedlineKato, Mai Yamaguchi, Momoka Ooka, Akira Takahashi, Ryota Suzuki, Takuji Onoda, Keita Yoshikawa, Yuko Tsunematsu, Yuta Sato, Michio Yoshioka, Yasukiyo Igarashi, Miki Hayakawa, Sumio Shoji, Kumiko Shoji, Yutaka Ishikawa, Tomohisa Watanabe, Kenji Miyoshi, Noriyuki eng Research Support, Non-U.S. Gov't England 2023/06/02 Sci Rep. 2023 Jun 1; 13(1):8924. doi: 10.1038/s41598-023-36091-7"