Lifestyle-related diseases including obesity may lead to severe conditions such as cardiovascular disease. FGF19 and FGF21, expressed in the small intestine and liver, respectively, are anti-obesity hormone-like molecules. In this study, we studied novel transcriptional regulation of the FGF19 and FGF21 genes with the aim of establishing a research base for functional food factors that might prevent metabolic syndrome. Experiments using intestinal cell lines revealed that endoplasmic reticulum stress regulates expression of the FGF19 gene, and that FGF19 is a novel target gene of the transcription factor ATF4, which is activated by endoplasmic reticulum stress. We also found that ATF4 also regulates expression of the FGF21 gene as well as the FGF19 gene. ATF4 is activated by a variety of stimuli in addition to endoplasmic reticulum stress. Experiments using cell lines and mice showed that expression of the FGF19 and FGF21 genes is selectively regulated by these stimuli. These results suggest that ATF4 is a novel regulator of FGF19 and FGF21 gene expression, and a potential target molecule for prevention of metabolic syndrome.

Rice is a staple food and has importance as a protein source as well as a major energy source in Japan. However, data about the physiological functions of rice protein remain limited, despite its importance. We have therefore investigated the various physiological functions of rice protein. First, we conducted an in vivo digestion test of rice endosperm protein to clarify the digestibility of rice prolamin. Our in vivo experiments showed that the digestibility of rice prolamin is decreased by cooking but is improved by alkali extraction. Furthermore, our investigation of alkali-extracted rice endosperm protein (AE-REP) revealed that it reduces plasma total cholesterol, hepatic total cholesterol, and hepatic triglycerides, as well as ameliorating diabetic nephropathy in diabetic model rats.

To investigate the effects of diet restriction on glucose and lipid metabolism, indicator molecules were measured at 3-h intervals beginning at 18:00 in rats that were fed at 17:00, after feeding ad libitum (control) , or after feeding on 80% of the control diet for 2 weeks. Stomach contents were increased in the diet restriction group relative to the control group until 3:00 next morning and then decreased after 9:00. In the diet restriction group, the levels of plasma free fatty acid and total ketone body increased and the level of insulin decreased during fasting. The hepatic glycogen level reached a peak similarly to the control group at 7 h after feeding but 6 h earlier than in the control group. As a result of diet restriction, the plasma and liver triacylglycerol levels were significantly decreased and the weights of visceral adipose tissue were significantly decreased with a decrease of body weight increment. The diurnal rhythm was generally more obvious in the diet restriction group than in the control group. In the diet-restricted rats, the plasma corticosterone concentration was significantly increased and the indices of glucose and lipid metabolism were similar during starvation, suggesting that the diet-restricted rats could not avoid stress shortly before receiving the next meal at 17:00.