title: Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice.
abstract: 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.
authors.affiliation: Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tsuneyuki
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.|Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shirakami
authors.affiliation: Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Ideta
authors.affiliation: Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kochi
authors.affiliation: Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: Department of Gastroenterology/Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D000464:Alginates / Q000627:therapeutic use*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D004052:Diethylnitrosamine; D020723:Glucuronic Acid / Q000627:therapeutic use; D006603:Hexuronic Acids / Q000627:therapeutic use; D006946:Hyperinsulinism; D007249:Inflammation / Q000188:drug therapy; D007333:Insulin Resistance; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000473:pathology; D009765:Obesity / Q000188:drug therapy* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D004052:Diethylnitrosamine; D020723:Glucuronic Acid
keywords: diabetes mellitus; liver carcinogenesis; non-alcoholic steatohepatitis; obesity; sodium alginate