Excessive eating and underexercising has been caused hyperlipidemia in recent years. Soy food especially soymilk, has been expected to prevent hyperlipidemia. In the thesis, The author focused on new physiological effects of soymilk and lactic acid-fermented soymilk on lipid metabolism-modulation in liver. The effects of lactic acid-fermented soymilk containing okara on the plasma and hepatic lipid profiles, and expression of the lipid metabolism-related genes in rats were previously reported. Additionally, the dose of soymilk for improving lipid metabolisum was also reported. However, the dose of fermented soymilk for improving lipid metabolism has not been solved. Therefore, the dose of fermented soymilk for improving lipid metabolism was found in the chapter 1. The administration of amount of fermented soymilk corresponding to more than 10% soy protein in diet was necessary to keep a significant physiological effects during about 1 month. In the chapter 2, the different effects between soymilk and fermented soymilk on lipid metabolism and lipid metabolism-related gene expression were clarifaied through the regulation of hepatic gene expression induced by the ingestion of lactic acid-fermented soymilk. Soymilk and fermented soymilk down-regulated the expression of hepatic fatty acid synthesis-related gene to reduce the hepatic TG level in rats. Hepatic cholesterol level of the soymilk and fermented soymilk groups were also decreased vs. that of C proup. Especially, the ingestion of fermented soymilk induced the up-regulation of hepatic CYP7a1 and then reduced the plasma cholesterol level in rats compared with that of soymilk. Therefore, the bioactive components produced by lactic acid fermentation, isoflavone and others, seemed to induce the up-regulation of hepatic CYP7a1 to reduce the plasuma cholesterol level in rats. Although the lipid metabolism-modulating effect of soy protein has mostly been clarified, that of isoflavone is still less obvious. Therefore, the author noted isoflavone as bioactive component on lipid metabolism-modulating effect. In the chapter 3, the relationships between the ratio of the isoflavone aglycone in total isoflavone and with or without soy protein in fermented soymilk were investigated to clarify lipid metabolism-modulation effects in rats fed a cholesterol-free diet. Thus the aglyconized isoflavone coexsisted with soy protein markedly reduced hepatic lipid level. Therefore, it was assumed that both of aglyconaized isoflavone and soy protein enhanced lipid metabolism-modulation in rats ingested fermented soymilk. Moreover, it was suggested that isoflavone not only the up-regulated of CYP7a1 expression but also increased cholesterol synthesis-related gene expression. On the other hand, soy protein reduced the expression of fatty acid synthesis-related gene. These results indicated that isofulavones and soy proteins have different roles on lipid metabolism from each other and isoflavone aglycone enhances lipid metabolism-modulation by coexistence with soy protein. Recently, hyperlipidemia is known to be induced by cholesterol-rich diet is a severe problem. Thus, in the chapter 4, hypocholesterolemic effect of fermented soymilk on rats fed a high cholesterol diet was investigated. It was assumed that the fermented soymilk induced the down-regulation of SREBP-2 and up-regulation of CYP7a1 to modulate the cholesterol metabolism in rats fed a high cholesterol diet. In the chapter 5 and 6, The author investigated the effect of aglycone ratio of isoflavone in fermented soymilk on lipid metabolism. The different isoflavone aglycone ratios in lactic acid-fermented soymilk differently affected the hepatic lipid metabolism in rats fed a high cholesterol diet and lipid loading test. It was found that the modulation function was stronger in fermented soymilk including high aglycone ratio of isoflavone than in that including low aglycone ratio of isoflavone. Isoflavone converted from glycone to aglycone by lactic acid-fermenteation seems to promote the intestinal absorption and increase hepatic concentration of isoflavone. Therefore, it was suggested that fermented soymilk containing high ratio of isoflavone aglycone promoted lipid metabolism-modulating effects. In the present studies, fermented soymilk exhibited lipid metabolism-modulating effect in all rats fed an AIN-93G diet, high cholesterol diet and lipid loading test. Additionally, aglyconized isoflavone coexsisted with soy protein markedly reduced hepatic lipid. Therefore, it is suggested that fermented soymilk containing both of aglyconaized isoflavone and soy protein enhanced lipid metabolism-modulation, because higher ratio of isoflavone aglycone in fermented soymilk had stronger lipid metabolism-modulating effect vs. lower ratio of isoflavone aglycone in fermented soymilk, Thus, it is assumed that fermented soymilk has primary prevention effect of hyperlipidemia induced by excessive eating and underexercising. Hence, it is concluded that fermented soymilk containing abundant soy protein and isoflavone aglycone is suitable for hepatic lipid metabolisum-modulating food. The intake of fermented soymilk might contribute to prevent metabolic syndrome such as fatty liver.

2013