Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Ibaraki 305-8575, Japan.
Biochem Biophys Res Commun. 2010 Jan 8;391(2):1222-7. doi: 10.1016/j.bbrc.2009.12.046. Epub 2009 Dec 16.
To elucidate the physiological role of CREBH, the hepatic mRNA and protein levels of CREBH were estimated in various feeding states of wild and obesity mice. In the fast state, the expression of CREBH mRNA and nuclear protein were high and profoundly suppressed by refeeding in the wild-type mice. In ob/ob mice, the refeeding suppression was impaired. The diet studies suggested that CREBH expression was activated by fatty acids. CREBH mRNA levels in the mouse primary hepatocytes were elevated by addition of the palmitate, oleate and eicosapenonate. It was also induced by PPARalpha agonist and repressed by PPARalpha antagonist. Luciferase reporter gene assays indicated that the CREBH promoter activity was induced by fatty acids and co-expression of PPARalpha. Deletion studies identified the PPRE for PPARalpha activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay confirmed that PPARalpha directly binds to the PPRE. Activation of CREBH at fasting through fatty acids and PPARalpha suggest that CREBH is involved in nutritional regulation.
为了阐明 CREBH 的生理作用，我们评估了野生型和肥胖型小鼠在不同进食状态下肝脏中 CREBH 的 mRNA 和蛋白水平。在禁食状态下，野生型小鼠的 CREBH mRNA 和核蛋白表达水平较高，并在再次进食时受到强烈抑制。在 ob/ob 小鼠中，这种再进食抑制作用受损。饮食研究表明，脂肪酸激活了 CREBH 的表达。在小鼠原代肝细胞中，添加棕榈酸、油酸和二十碳五烯酸可升高 CREBH mRNA 水平。它也可被过氧化物酶体增殖物激活受体 alpha 激动剂诱导，被过氧化物酶体增殖物激活受体 alpha 拮抗剂抑制。荧光素酶报告基因分析表明，脂肪酸和过氧化物酶体增殖物激活受体 alpha 共表达可诱导 CREBH 启动子活性。缺失研究确定了 PPARalpha 激活的 PPRE。电泳迁移率变动分析和染色质免疫沉淀（ChIP）分析证实了过氧化物酶体增殖物激活受体 alpha 直接结合到 PPRE 上。在禁食状态下，脂肪酸和过氧化物酶体增殖物激活受体 alpha 的激活表明 CREBH 参与了营养调节。
