Research Papers:

Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice

Tsuneyuki Miyazaki _, Yohei Shirakami, Masaya Kubota, Takayasu Ideta, Takahiro Kochi, Hiroyasu Sakai, Takuji Tanaka, Hisataka Moriwaki and Masahito Shimizu

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Oncotarget. 2016; 7:10448-10458. https://doi.org/10.18632/oncotarget.7249

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Tsuneyuki Miyazaki1, Yohei Shirakami1,2, Masaya Kubota1, Takayasu Ideta1, Takahiro Kochi1, Hiroyasu Sakai1, Takuji Tanaka3, Hisataka Moriwaki1, Masahito Shimizu1

1Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan

2Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan

3Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan

Correspondence to:

Yohei Shirakami, e-mail: [email protected]

Keywords: obesity, non-alcoholic steatohepatitis, liver carcinogenesis, sodium alginate, diabetes mellitus

Received: November 24, 2015    Accepted: January 25, 2016    Published: February 08, 2016


Obesity and related metabolic abnormalities play a key role in liver carcinogenesis. Non-alcoholic steatohepatitis (NASH), which is often complicated with obesity and diabetes mellitus, is associated with the development of hepatocellular carcinoma (HCC). Sodium alginate (SA), which is extracted from brown seaweeds, is marketed as a weight loss supplement because of its high viscosity and gelling properties. In the present study, we examined the effects of SA on the progression of NASH and related liver carcinogenesis in monosodium glutamate (MSG)-treated mice, which show obesity, diabetes mellitus, and NASH-like histopathological changes. Male MSG-mice were intraperitoneally injected with diethylnitrosamine at 2 weeks of age, and, thereafter, they received a basal diet containing high- or low-molecular-weight SA throughout the experiment (16 weeks). At sacrifice, control MSG-treated mice fed the basal-diet showed significant obesity, hyperinsulinemia, steatosis and hepatic tumor development. SA administration suppressed body weight gain; improved insulin sensitivity, hyperinsulinemia, and hyperleptinemia; attenuated inflammation in the liver and white adipose tissue; and inhibited hepatic lipogenesis and progression of NASH. SA also reduced oxidative stress and increased anti-oxidant enzyme levels in the liver. Development of hepatic tumors, including liver cell adenoma and HCC, and hepatic pre-neoplastic lesions was significantly inhibited by SA supplementation. In conclusion, oral SA supplementation improves liver steatosis, insulin resistance, chronic inflammation, and oxidative stress, preventing the development of liver tumorigenesis in obese and diabetic mice. SA may have ability to suppress steatosis-related liver carcinogenesis in obese and diabetic subjects.

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