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Published in: BMC Gastroenterology 1/2020

Open Access 01-12-2020 | Obesity | Research article

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

Authors: Atsuko Takai, Kentaro Kikuchi, Mayuko Ichimura, Koichi Tsuneyama, Yuki Moritoki, Kotaro Matsumoto, Hiromichi Tsunashima, Takeshi Onda, Noriyuki Kuniyoshi, Tomoyuki Nariyama, Sho Ohyatsu, Juri Kubota, Kozue Nagumo, Shinpei Sato, Masumi Hara, Hiroshi Miyakawa

Published in: BMC Gastroenterology | Issue 1/2020

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production.
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Metadata
Title
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
Authors
Atsuko Takai
Kentaro Kikuchi
Mayuko Ichimura
Koichi Tsuneyama
Yuki Moritoki
Kotaro Matsumoto
Hiromichi Tsunashima
Takeshi Onda
Noriyuki Kuniyoshi
Tomoyuki Nariyama
Sho Ohyatsu
Juri Kubota
Kozue Nagumo
Shinpei Sato
Masumi Hara
Hiroshi Miyakawa
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2020
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-020-01194-2

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