IS CCAAT/ENHANCER-BINDING PROTEIN A CENTRAL REGULATOR OF ENERGY-METABOLISM
IS CCAAT/ENHANCER-BINDING PROTEIN A CENTRAL REGULATOR OF ENERGY-METABOLISM
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DOI：
10.1101/gad.3.12b.2021
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发表时间：
1989-12-01
影响因子：
10.5
通讯作者：
GLUECKSOHNWAELSCH, S
中科院分区：
文献类型：
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作者：
MCKNIGHT, SL;LANE, MD;GLUECKSOHNWAELSCH, S
长期以来，脊椎动物血糖水平的控制一直是临床和基础研究人员感兴趣的一个基本问题。人们对调节碳水化合物和脂肪代谢的循环激素（如胰岛素、胰高血糖素和糖皮质激素）了解甚多。这些激素的结构已经确定，它们的受体已经确定，总的来说，它们的作用方式已经被理解。同样，关于控制糖异生以及糖原和甘油三酯的合成和动员的激素调节酶，也积累了大量的信息。磷酸烯醇丙酮酸羧激酶（PEPCK）、葡萄糖激酶（GK）、酪氨酸转氨酶（TAT）、激素敏感脂肪酶（HSL）和甘油-3-磷酸脱氢酶（GPDH）等酶的氨基酸序列是已知的，其编码基因已被克隆。能量稳态问题的一个核心问题涉及肝脏和脂肪组织的分化，它们分别是碳水化合物和脂肪代谢的主要部位。肝脏是如何成为主要负责糖异生和糖原储存和动员的器官的？脂肪组织如何成为甘油三酯的储存库？这两个组织提供主要的循环生理燃料（葡萄糖、游离脂肪酸和酮类）。什么机制促进糖异生酶和脂肪生成酶在这些组织中的表达水平升高？这些酶的活动是如何受到控制血糖水平的激素的调节的呢？其中一些问题的答案正开始浮出水面。例如，肝脏中PEPCK、GK和TAT酶活性的丰度与其mRNA水平的相对升高相关。同样，GPDH和HSL转录本选择性地在分化的脂肪细胞中积累。是什么导致编码这些mrna的基因在适当的细胞类型中以较高的水平表达？此外，在肝细胞中表达受激素调节的PEPCK、GK、TAT和葡萄糖-6-磷酸酶（G-6-P）基因与在肝细胞中表达不受调节能量稳态的循环因子调节的其他基因有何区别？在本文中，我们推测能量平衡的调节可能至少部分是通过最近发现的一种称为CCAAT/增强子结合蛋白（C/EBP）的基因调节蛋白进行的。的
The control of blood glucose levels in vertebrates is a fundamental problem that has long intrigued both clinical and basic researchers. Much is known of the circulating hormones (eg, insulin, glucagon, and glucocorticoid) that regulate the metabolism of carbohydrate and fat. The structures of these hormones have been determined, their receptors identified, and in general terms, their modes of action are understood. Likewise, considerable information has accumulated concerning the hormone-regulated enzymes involved in the control of gluconeogenesis and the synthesis and mobilization of glycogen and triglycerides. The amino acid sequences of many of these enzymes, such as phosphoenolpyruvate carboxykinase (PEPCK), glucokinase (GK), tyrosine aminotransferase (TAT), hormone-sensitive lipase (HSL), and glycerol-3-phosphate dehydrogenase (GPDH) are known, and their encoding genes have been cloned. One issue central to the problem of energy homeostasis concerns the differentiation of liver and adipose tissues, respectively, as the principal sites of carbohydrate and fat metabolism. How does the liver become specified as the organ primarily responsible for gluconeogenesis and the storage and mobilization of glycogen? How does adipose tissue become the storage depot of triglycerides? Both tissues provide the major circulating physiological fuels (glucose, free fatty acids, and ketones). What mechanisms facilitate the elevated levels of expression of gluconeogenic and lipogenic enzymes in these respective tissues? How do these enzymatic activities become subject to regulation by the hormones that control blood sugar levels?The answers to some of these questions are beginning to emerge. For example, the abundance of PEPCK, GK, and TAT enzymatic activities in liver is correlated with relative increases in their mRNA levels. Likewise, GPDH and HSL transcripts accumulate selectively in differentiated adipocytes. What causes the genes encoding these mRNAs to be expressed at elevated levels in the appropriate cell types? Moreover, what distinguishes the PEPCK, GK, TAT, and glucose-6-phosphatase (G-6-P) genes, whose expression in liver cells is regulated hormonally, from other genes expressed in hepatocytes that are not responsive to regulation by the circulating factors that modulate energy homeostasis? In this communication we speculate that regulation of energy balance may be channeled, at least in part, through a recently discovered gene regulatory protein, termed CCAAT/enhancer-binding protein (C/EBP). The