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Influence Of Hyperglycemia On Liver Inflammatory Conditions In The Early Phase Of Non-alcoholic Fatty Liver Disease In Mice

Shinichi Harada, Kei Miyagi, Tokio Obata, Yasuko Morimoto, Kazuo Nakamoto, Ke Ih Kim, Soo Ki Kim, Soo Ryang Kim, Shogo Tokuyama

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Abstract Objectives A non-alcoholic fatty liver disease (NAFLD) has high prevalence and now important issue of public health. In general, there exists strong interaction between NAFLD and diabetes, but the detailed mechanism is unclear. In this study, we determined the effects of hyperglycemia on progression in the early phase of NAFLD in mice. Methods Male ddY mice were fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) consisting of 60% of kcal from fat and 0.1% methionine by weight. Hyperglycemic condition was induced by streptozotocin (STZ) treatment. The assessment of liver function used serum AST and ALT levels, and histological analysis. Hepatic tumour necrosis factor (TNF)-α mRNA levels was estimated by qRT-PCR. Key findings During the 3–42 days that the mice were fed CDAHFD, the livers gradually caused accumulation of fat, and infiltration of inflammation cells gradually increased. Serum AST and ALT levels and significantly increased after being fed CDAHFD for 3 days and were exacerbated by the STZ-induced hyperglycemic condition. In addition, hepatic TNF-α mRNA also significantly increased. These phenomena reversed by insulin administration. Conclusions The results showed that progression in the early phase of NAFLD may be exacerbated by hyperglycemia-induced exacerbation of inflammation.