Phosphoenolpyruvate carboxykinase is necessary for the integration of hepatic energy metabolism
Phosphoenolpyruvate carboxykinase is necessary for the integration of hepatic energy metabolism
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DOI：
10.1128/mcb.20.17.6508-6517.2000
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发表时间：
2000-09-01
影响因子：
5.3
通讯作者：
Magnuson, MA
中科院分区：
文献类型：
--
作者：
She, P;Shiota, H;Magnuson, MA
我们在小鼠中使用等位基因Cre/loxP基因靶向策略来确定胞质磷酸烯醇式丙酮酸羧激酶（PEPCK）在肝脏能量代谢中的作用。缺乏这种酶的小鼠在出生后3天内死亡，而PEPCK总体减少至少90%或肝脏特异性敲除PEPCK的小鼠是可行的。令人惊讶的是，在这两种情况下，这些动物在禁食24小时后仍保持血糖正常。然而，没有肝脏PEPCK的小鼠在禁食后发生肝脂肪变性，尽管编码脂肪酸氧化酶的多种基因上调。此外，参与能量代谢的肝脏基因表达的显著改变发生在血浆激素浓度没有任何变化的情况下。鉴于肝脏特异性PEPCK敲除小鼠的肝脏苹果酸浓度升高了9倍，我们认为一种或多种中间代谢产物可能直接调节受影响基因的表达。因此，肝脏PEPCK可能更多地作为肝脏能量代谢的整合者而不是作为肝再生的决定因素。
We used an allelogenic Cre/loxP gene targeting strategy in mice to determine the role of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in hepatic energy metabolism. Mice that lack this enzyme die within 3 days of birth, while mice with at least a 90% global reduction of PEPCK, or a liver-specific knockout of PEPCK, are viable. Surprisingly, in both cases these animals remain euglycemic after a 24-h fast. However, mice without hepatic PEPCK develop hepatic steatosis after fasting despite up-regulation of a variety of genes encoding fi ee fatty acid-oxidizing enzymes. Also, marked alterations in the expression of hepatic genes involved in energy metabolism occur in the absence of any changes in plasma hormone concentrations. Given that a ninefold elevation of the hepatic malate concentration occurs in the liver-specific PEPCK knockout mice, we suggest that one or more intermediary metabolites may directly regulate expression of the affected genes. Thus, hepatic PEPCK may function more as an integrator of hepatic energy metabolism than as a determinant of gluconeogenesis.