ＭＺＴ（株）ゼブラフィッシュ創薬研究所

Novel Non-Alcoholic Fatty Liver Model for Systems Pharmacology

第87回日本生化学会

Michiko Ariyoshi1, Yuhei Nishimura1, Noriko Umemoto1, Yasuhito Shimada1, Takehiko Oka2, Junya Kuroyanagi2, Atsushi Midorikawa2,Kozo Kawahara2, Toshio Tanaka11.Department of Pharmacogenomics and Systems Pharmacology, Mie University Graduate School of Medicine, 2.World Fusion Co.,Ltd

The prevalence of obesity has increased seriously in developed countries. Such
estimates are particularly alarming given the strong association between obesity and
various adverse health consequences, such as atherosclerosis, hypertension, type2
diabetes abd certain types of cancer. We established a zebrafish model of diet-induced
obesity that shared common pathophysiological pathways with mammalian obesity
(BMC Physiology 2010).

Then we examined the effects of eriocitrin(Sci Rep.2014), green tea extract(Nutr Metab 2012) or Campari tomato(Nutr Metab 2011) on the obesity model and transcriptome. And we found that both eriocitrin and Campari tomato prevents diet-induced hyperlipidemia and hepatic steatosis. Moreover, Campari tomato suppressed increase of body weight in diet-induced obesity model and not with eriocitrin.

Eriocitrin(eriodictyol 7-rutinoside) is a major flavonoid with antioxidant activity of all the
bioactive molecules of lemon. Eriocitrin has a suppressive effect on oxidative stress in
diabetic rats and a lipid-lowering effect in rats on high-fat and high-cholesterol diets.
However, the mechanism of regulation of hepatic lipid metabolism by eriocitrin has yet
to be elucidated. We have done comparative transcriptomics analysis on pharmacology
of eriocitrin, Campari tomato, green tea extract or calorie restriction in the obesity model.

Systems approaches have been used in pharmacology to understand eriocitrin action at
the organ level. The application of computational and experimental systems biology
approaches to pharmacology allows us to expand the definition of systems
pharmacology to include network analyses at multiple scales of biological organization
and to explain preventive effects of eriocitrin.

Systems pharmacology analyses rely on experimental “omics” technologies that are capable of measuring changes in large numbers of variables, often at a genome-wide level, to build networks for analyzing eriocitrin action on the non-alcoholic fatty liver model

ＭＺＴ（株）ゼブラフィッシュ創薬研究所

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Novel Non-Alcoholic Fatty Liver Model for Systems Pharmacology

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