Research for usefulness of intestinal peptide, PYY_<3-36> for therapeutic agents of fatty liver and NASH

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We examined the therapeutic effects of PYY_<3-36> on model animals showing obesity and fatty liver. Firstly, we studies using Zucker obesity model rats, and observed the effects of PYY_<3-36> in these rats. That is, 0-5μg/100g PYY per day was injected intraperitonialy for 30 days, and measured body weight point by point during observation term. In results, the increase of body weight of rats in the group treated with 5μg/100g PYY was significantly suppressed compared with that in the control group without treatment with PYY. However, nonalcoholic fatty liver diseases (NAFLD) containing nonalcoholic steatohepatitis (NASH) were not observed in liver tissues of these model rats. Next, we added the high calorie diet to the Zucker model rats for 1 month, and the characteristic findings of NASH such as intralobular inflammation, ballooning hepatocytes and Mallory's bodies were observed in the liver specimens. On the other hands, the histological findings of NASH were hardly observed in livers of the PYY-treated groups. However, the improvement of body weight was not recognized with PYY-treatment in this model rats, and we gave up a clinical trial, which treats with PYY in the patients with NAFLD and obesity.Just at that moment, we reported that transgenic (Tg) mice which over express nSREBP-1c (nuclear sterol regulatory element-binding protein 1c) in fat tissues cause NASH. We examined the effects of green tea (-)-epigallocatechin-3-gallate (EGCG) in this nSREBP-1 Tg NASH model mice. That is, Water containing 0.05-0.1% EGCG was orally administrated for 3 months. In results, the increases of body weight and liver weight, and the progression of NASH were significantly suppressed with treatment of EGCG. Presently, we are studying whether the improvement of lipids, oxidative stress, insulin resistance and inflammation in the liver tissues are brought with EGCG treatment in the model mice.