Fructo-oligosaccharides ameliorate steatohepatitis, visceral adiposity, and associated chronic inflammation via increased production of short-chain fatty acids in a mouse model of non-alcoholic steatohepatitis

• Published in: BMC gastroenterology 2020-02, Vol.20 (1), p.46-46, Article 46
• Main Authors: Takai, Atsuko, Kikuchi, Kentaro, Ichimura, Mayuko, Tsuneyama, Koichi, Moritoki, Yuki, Matsumoto, Kotaro, Tsunashima, Hiromichi, Onda, Takeshi, Kuniyoshi, Noriyuki, Nariyama, Tomoyuki, Ohyatsu, Sho, Kubota, Juri, Nagumo, Kozue, Sato, Shinpei, Hara, Masumi, Miyakawa, Hiroshi
• Format: Article
• Language: English
• Subjects: Acetic acid; Adipose tissue; Age; Animals; Cancer; Carcinoma; Care and treatment; Deoxyribonucleic acid; Development and progression; Diabetes; Diet; Disease Models, Animal; Diseases; DNA; Drinking water; Enzymes; Fatty acid synthesis; Fatty acids; Fatty Acids, Volatile - metabolism; Fatty liver; Feces; Fibrosis; Fructo-oligosaccharides; Fruit; Gastroenterology; Gene expression; Glutamate; Glycerol; Health aspects; Hepatocellular carcinoma; House mouse; Inflammation; Liver; Liver cirrhosis; Liver diseases; Macrophages; Male; Medical research; Messenger RNA; Mice; Mice, Inbred C57BL; Monosodium glutamate; Newborn infants; Non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - diet therapy; Non-alcoholic steatohepatitis; Obesity; Obesity, Abdominal - diet therapy; Oligosaccharides; Oligosaccharides - administration & dosage; Oligosaccharides - pharmacology; Organic acids; Phosphates; RNA; Saturated fatty acids; Short-chain fatty acids; Type 2 diabetes; Water
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/s12876-020-01194-2

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH. Twelve newborn C57BL/6 J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured. Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 μmol/L, P = 0.001). FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production.