Sterol regulatory element binding protein (SREBP)-1 expression in brain is affected by age but not by hormones or metabolic changes
Sterol regulatory element binding protein (SREBP)-1 expression in brain is affected by age but not by hormones or metabolic changes
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DOI：
10.1016/j.brainres.2006.01.081
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发表时间：
2006-04-07
期刊：
影响因子：
2.9
通讯作者：
Yoshimatsu, H
中科院分区：
文献类型：
--
作者：
Okamoto, K;Kakuma, T;Yoshimatsu, H
固醇调节元件结合蛋白（SREBP）-1是一种膜结合转录因子，调节包括肝脏在内的外周组织中参与细胞脂肪酸合成的几个基因的表达。虽然SREBP-1在脑中表达，但对其功能知之甚少。本研究的目的是阐明不同营养和激素条件下大鼠脑SREBP-1 mRNA表达的特点。在遗传性肥胖（fa/fa）Zucker大鼠中，与这些大鼠的瘦同窝仔相比，SREBP-1 mRNA在肝脏中的表达高于下丘脑或大脑。禁食45小时和再喂养3小时不影响Wistar大鼠脑中SREBP-1 mRNA或作为SREBP-1靶点的脂肪生成酶的mRNA的表达，即，脂肪酸合酶（FAS）和乙酰辅酶A羧化酶（ACC）。第三脑室注射2.0 mIU胰岛素或3.0 μ g瘦素不影响下丘脑或大脑中SREBP-1 mRNA的表达。过表达瘦素的转基因小鼠脑中SREBP-1 mRNA的表达与野生型小鼠没有差异。然而，我们观察到一个独特的年龄相关的变化SREBP-1 mRNA表达的Sprague-Dawley大鼠的大脑。具体而言，SREBP-1 mRNA表达在1至20月龄之间增加，而FAS或ACC的表达没有这种变化。这提出了一种可能性，即SREBP-1表达的增加继发于与衰老相关的多不饱和脂肪酸（PUFA）下降，可能会补偿FAS表达的减少。这些结果表明，SREBP-1和下游脂肪生成酶在脑中的表达可能不受外周营养条件或体液因素的调节。SREBP-1 mRNA表达的增龄性变化可能参与脑脂质代谢的发育变化。(c)2006 Elsevier B. V.保留所有权利。
Sterol regulatory element binding protein (SREBP)-1 is a membrane-bound transcription factor that regulates the expression of several genes involved in cellular fatty acid synthesis in the peripheral tissues, including liver. Although SREBP-1 is expressed in brain, little is known about its function. The aim of the present study was to clarify the characteristics of SREBP-1 mRNA expression in rat brain under various nutritional and hormonal conditions. In genetically obese (fa/fa) Zucker rats, expression of SREBP-1 mRNA was greater in liver than in hypothalamus or cerebrum compared to the lean litter-mates of these rats. Fasting for 45 h and refeeding for 3 h did not affect expression in brains of Wistar rats of SREBP-1 mRNA or the mRNAs of lipogenic enzymes that are targets of SREBP-1, i.e., fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). Infusion of 2.0 mIU insulin or 3.0 mu g leptin into the third cerebroventricle did not affect SREBP-1 mRNA expression in either hypothalamus or cerebrum. SREBP-1 mRNA expression in brains of transgenic mice that overexpressed leptin did not differ from that of wild-type mice. However, we observed a unique age-related alteration in SREBP-1 mRNA expression in brains of Sprague-Dawley rats. Specifically, SREBP-1 mRNA expression increased between 1 and 20 months of age, while there was no such change in the expression of FAS or ACC. This raises the possibility that increased SREBP-1 expression secondary to aging-related decline of polyunsaturated fatty acid (PUFA) might compensate for the reduction of FAS expression in brain. These findings suggest that the expression of SREBP-1 and downstream lipogenic enzymes in brain is probably not regulated by peripheral nutritional conditions or humoral factors. Aging-related changes in SREBP-1 mRNA expression may be involved in developmental changes in brain lipid metabolism. (c) 2006 Elsevier B.V. All rights reserved.