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首页> 外文期刊>American Journal of Physiology >The role of chicken ovalbumin upstream promoter transcription factor II in the regulation of hepatic fatty acid oxidation and gluconeogenesis in newborn mice
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The role of chicken ovalbumin upstream promoter transcription factor II in the regulation of hepatic fatty acid oxidation and gluconeogenesis in newborn mice

机译：鸡卵体上游启动子转录因子II在新生儿小鼠中肝脂肪酸氧化和葡糖生成调控中的作用

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Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan nuclear receptor involved in the control of numerous functions in various organs (organogenesis, differentiation, metabolic homeostasis, etc.). The aim of the present work was to characterize the regulation and contribution of COUP-TFII in the control of hepatic fatty acid and glucose metabolisms in newborn mice. Our data show that postnatal increase in COUP-TFII mRNA levels is enhanced by glucagon (via cAMP) and PPARa. To characterize COUP-TFII function in the liver of suckling mice, we used a functional (dominant negative form; COUP-TFII-DN) and a genetic (shRNA) approach. Adenoviral COUP-TFII-DN injection induces a profound hypoglyce-mia due to the inhibition of gluconeogenesis and fatty acid oxidation secondarily to reduced PEPCK, Gl-6-Pase, CPT I, and mHMG-CoA synthase gene expression. Using the crossover plot technique, we show that gluconeogenesis is inhibited at two different levels: 1) pyruvate carboxylation and 2) trioses phosphate synthesis. This could result from a decreased availability in fatty acid oxidation arising cofactors such as acetyl-CoA and reduced equivalents. Similar results are observed using the shRNA approach. Indeed, when fatty acid oxidation is rescued in response to Wy-14643-induced PPARa target genes (CPT I and mHMG-CoA synthase), blood glucose is normalized in COUP-TFII-DN mice. In conclusion, this work demonstrates that postnatal increase in hepatic COUP-TFII gene expression is involved in the regulation of liver fatty acid oxidation, which in turn sustains an active hepatic gluconeogenesis that is essential to maintain an appropriate blood glucose level required for newborn mice survival.
机译：鸡卵磷蛋白上游启动子转录因子II（Coup-TFII）是一种孤儿核受体，参与各种器官（有机组织，分化，代谢稳态等）中众多功能的控制。本作本作的目的是表征Coup-TFII对新生儿小鼠肝脂肪酸和葡萄糖代谢的调控和贡献。我们的数据显示，胰高血糖素（营地）和PPARA增强了COUP-TFII mRNA水平的后期增加。为了表征哺乳小鼠肝脏中的Coup-TFII功能，我们使用了功能（主导负面形式; Coup-TFII-DN）和遗传（shRNA）方法。腺病毒COUP-TFII-DN注射诱导由于葡糖生成和脂肪酸氧化的抑制而引起了深厚的低词糖，其次降低了PEPCK，GL-6-酶，CPT I和MHMG-COA合酶基因表达。使用交叉曲线技术，我们表明葡糖生成在两种不同水平下抑制：1）丙酮酸羧化和2）意味着磷酸盐合成。这可能是由于脂肪酸氧化的可用性降低而导致乙酰辅酶酸等乙酰基 - COA和降低的等同物。使用ShRNA方法观察到类似的结果。实际上，当响应于WY-14643诱导的PPARA靶基因（CPT I和MHMG-COA合酶）来拯救脂肪酸氧化时，血糖在COUP-TFII-DN小鼠中归一化。总之，这项工作表明，肝脏COUP-TFII基因表达的出生后增加参与肝脂肪酸氧化的调节，这反过来依次维持活性肝葡糖生成，这对于维持新生小鼠生存所需的适当血糖水平至关重要。

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