| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2005: ¥9,100,000 (Direct Cost: ¥9,100,000)
|
|---|
| Research Abstract |
In thee liver and small intestine, major organs for lipid metabolism, lipid homeostasis is under the precision transcriptional control. Indeed, the activities of a number of enzymes involved in lipid metabolism undergo a dramatic change at the transcriptional levels during fasting and refed conditions. In the current study we investigate the crosstalk between transcription factors and some nuclear receptors controlling lipid metabolism in the liver cells. In addition, we analyze functions of FXR, a member of nuclear receptors, in the small intestine. We found that SREBPs, major transcription factors maintaining lipid homeostasis in the liver, can interact with some nuclear receptors that are also involved in regulation of lipid metabolism, thereby controlling their transcriptional activities reciprocally. In particular, LRH-1, a nuclear receptor controlling bile acid homeostasis, is a novel candidate that SREBPs can regulate its transcriptional activities. It is likely that this interaction regulates bile acid synthesis. Furthermore, we found that FXR and BABP, bile acid-binding protein, are functionally co-working in the intestinal cells through the mutual protein-protein interaction. As BABP is one of FXR target genes, this new finding provides us with a new feedforward concept that bile acids uptaken in the small intestine stimulate FXR functions through binding to BABP.
Based on the current findings, we are attempting to establish some assay systems evaluating food functions. Some food factors found through these assays can become potential candidates to produce functional foods that prevent some life-style related diseases.
|
