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.