Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice.
Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice.
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DOI：
10.18632/oncotarget.7249
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Shimizu M
中科院分区：
文献类型：
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作者：
Miyazaki T;Shirakami Y;Kubota M;Ideta T;Kochi T;Sakai H;Tanaka T;Moriwaki H;Shimizu M
肥胖及相关代谢异常在肝癌发生中起关键作用。非酒精性脂肪性肝炎（NASH）常并发肥胖和糖尿病，与肝细胞癌（HCC）的发展有关。海藻酸钠（SA）是从褐色海藻中提取的，由于其高粘度和胶凝特性，被作为减肥补充剂销售。在本研究中，我们研究了SA对味精处理小鼠NASH进展和相关肝癌发生的影响，这些小鼠表现出肥胖、糖尿病和NASH样组织病理改变。雄性msg小鼠在2周龄时腹腔注射二乙基亚硝胺，随后在整个实验期间（16周）给予含有高或低分子量SA的基础饲粮。在牺牲时，喂食基础饮食的对照组小鼠表现出明显的肥胖、高胰岛素血症、脂肪变性和肝肿瘤发展。SA给药抑制体重增加；改善胰岛素敏感性、高胰岛素血症和高瘦素血症；肝脏和白色脂肪组织炎症减轻；抑制肝脏脂肪生成和NASH进展。SA还能减少氧化应激，增加肝脏中的抗氧化酶水平。补充SA可显著抑制肝脏肿瘤的发展，包括肝细胞腺瘤和HCC，以及肝脏肿瘤前病变。综上所述，口服SA可改善肥胖和糖尿病小鼠的肝脏脂肪变性、胰岛素抵抗、慢性炎症和氧化应激，防止肝脏肿瘤的发生。SA可能具有抑制肥胖和糖尿病患者脂肪变性相关的肝癌发生的能力。
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.