Molecular pathological analysis of pathogenesis of non-alcoholic steatohepatitis: Propose of new treatment approach

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Metabolic syndrome is one of the most important disease conditions in all over the world. Severe and incurable diseases such as diabetes mellitus, arteriosclerosis and cerebro-vascular diseases were induced from lipid overdeposition in visceral fat. Recently, hepatic manifestation of metabolic syndrome was noted as non-alcoholic fatty liver diseases (NAFLD). Especially, non alcoholic steatohepatitis (NASH), which is severe phenotype of NAFLD is of a serious concern due to its increasing prevalence in the westernized world. Importantly, NASH may ultimately lead to the development of liver cirrhosis and hepatocellular carcinoma even in young generation. To make clarify the disease mechanism of NAFLD under the condition of obesity, we developed several unique animal models based on different disease condition. High-cholesterol fed rat and rabbit showed typical slender fibrosis as well as lipid overload in the liver, similar to human liver fibrosis. While Galectin-3 knock out mice, monosodium-glutamate treated mice and SHR/NDmcr-cp rats showed central obese, type 2 diabetes and marked fatty change with inflammation in predominant to male. We analyzed these animals showing NASH-like liver pathology as well as human liver specimens suffering NASH. In present study, we succeeded to clarify that lipid peroxidation, oxidative stress and glycation play important roles for disease progress of NASH. In addition, we made clarify the preventional roles of NASH using several traditional herval medicines. To find the effective products for metabolic syndrome including NASH is one of the most important contribution for primary care of peoples candidate of metabolic syndrome. We will continue to seek some effective natural products using our animal models.