Metabolic syndrome (MS) is a risk factor for
type 2 diabetes mellitus, vascular
inflammation,
atherosclerosis, and renal, liver, and
heart diseases. Non-
alcoholic steatohepatitis (NASH) is a progressive representative
liver disease and may lead to the irreversible calamities of
cirrhosis and
hepatocellular carcinoma. Metabolic disorders such as
hyperglycemia have been broadly reported to be related to hepatocarcinogenesis in NASH; however, direct evidence of a link between
hyperglycemia and
carcinogenesis is still lacking. Tsumura Suzuki Obese Diabetic (TSOD) mice spontaneously develop
metabolic syndrome, including
obesity,
insulin resistance, and NASH-like liver phenotype, and eventually develop
hepatocellular carcinomas. TSOD mice provide a spontaneous human MS-like model, even with significant individual variations. In this study, we monitored mice in terms of their changes in
blood glucose levels,
body weights, and pancreatic and liver lesions over time. As a result, liver
carcinogenesis was delayed in non-hyperglycemic TSOD mice compared to hyperglycemic mice. Moreover, at the termination point of 40 weeks, liver
tumors appeared in 18 of 24 (75%) hyperglycemic TSOD mice; in contrast, they only appeared in 5 of 24 (20.8%) non-hyperglycemic mice. Next, we investigated three kinds of
oligosaccharide that could lower
blood glucose levels in hyperglycemic TSOD mice. We monitored the levels of blood and urinary
glucose and assessed pancreatic lesions among the experimental groups. As expected, significantly lower levels of blood and urinary
glucose and smaller deletions of Langerhans cells were found in TSOD mice fed with milk-derived
oligosaccharides (galactooligosaccharides and
lactosucrose). At the age of 24 weeks, mild
steatohepatitis was found in the liver but there was no evidence of liver
carcinogenesis. Steatosis in the liver was alleviated in the milk-derived
oligosaccharide-administered group. Taken together, suppressing the increase in
blood glucose level from a young age prevented susceptible individuals from diabetes and the onset of
NAFLD/NASH, as well as
carcinogenesis. Milk-derived
oligosaccharides showed a lowering effect on
blood glucose levels, which may be expected to prevent liver
carcinogenesis.