Regulation of mitochondrial sn-glycerol-3-phosphate acyltransferase activity:: Response to feeding status is unique in various rat tissues and is discordant with protein expression
Regulation of mitochondrial sn-glycerol-3-phosphate acyltransferase activity:: Response to feeding status is unique in various rat tissues and is discordant with protein expression
复制标题
DOI：
10.1006/abbi.2001.2604
复制
发表时间：
2001-12-01
影响因子：
3.9
通讯作者：
Coleman, RA
中科院分区：
文献类型：
--
作者：
Lewin, TM;Granger, DA;Coleman, RA
三酰甘油在机体抵抗燃料匮乏的能力中起着关键作用，而三酰甘油合成的失调在肥胖和糖尿病等疾病的发展中起着重要的作用。甘油-3-磷酸酰基转移酶(GPAT)催化甘油脂合成的起始和关键步骤，因此是调节三酰甘油合成的潜在位点。由于一些研究表明三酰甘油的合成与线粒体的异构体有关，我们研究了线粒体GPAT的表达以及摄食状态对线粒体GPAT在不同组织中的调节的影响。肝脏、脂肪和比目鱼肌GPAT mRNA水平高，但蛋白表达低，而心脏和肾上腺GPAT mRNA丰度低的组织GPAT蛋白表达最高。此外，线粒体GPAT蛋白表达最高的心脏，线粒体GPAT比活性较低(0.02nmol/min/mg)。肝脏和脂肪具有最高的线粒体GPAT比活性(0.17nmol/min/mg)，但蛋白质表达很低。GPAT蛋白表达和活性的差异表明线粒体GPAT可能受到强烈的调控。禁食48小时后，肝脏和脂肪线粒体GPAT蛋白表达和活性下降30-50%。再投喂饲料或高糖饲料24小时后，线粒体GPAT蛋白表达和活性均超过正常水平30-60%。在肾脏，随着再投喂，线粒体GPAT蛋白和活性分别增加65%和30%，而在心脏，禁食后线粒体GPAT活性增加2.3倍，蛋白表达没有变化。我们还发现，新生大鼠肝脏线粒体GPAT活性占总GPAT活性的百分比低于成年大鼠。我们推测，GPAT的表达在每个组织中都是根据三酰甘油储存的特定需要而独特地调节的。(C)2001年爱思唯尔科学公司。
Triacylglycerol plays a critical role in an organism's ability to withstand fuel deprivation, and dysregulation of triacylglycerol synthesis is important in the development of diseases such as obesity and diabetes. Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the initial and committed step of glycerolipid synthesis and is therefore a potential site for regulation of triacylglycerol synthesis. Because several studies suggest that triacylglycerol synthesis is linked to the mitochondrial isoform, we studied mitochondrial GPAT expression and the effect of feeding status on the regulation of mitochondrial GPAT in various rat tissues. Liver, adipose, and soleus muscle have high levels of GPAT mRNA, but low protein expression, whereas heart and adrenal, tissues with low GPAT mRNA abundance, have the highest GPAT protein expression. In addition, heart, which has the highest expression of mitochondrial GPAT protein, has low mitochondrial GPAT specific activity (0.02 nmol/min/ mg). Liver and adipose have the highest mitochondrial GPAT specific activity (0.17 nmol/min/mg), but very low protein expression. Discrepancies between GPAT protein expression and activity suggest that mitochondrial GPAT may be regulated acutely. In response to a 48-h fast, liver and adipose mitochondrial GPAT protein expression and activity decrease 30-50%. After 24-h refeeding of either chow or high-sucrose diet, mitochondrial GPAT protein expression and activity overshoot normal levels 30-60%. In kidney, mitochondrial GPAT protein and activity increase 65 and 30%, respectively, with refeeding, whereas in the heart, mitochondrial GPAT activity increases 2.3-fold after a fast, with no change in protein expression. We also found that hepatic mitochondrial GPAT activity in the neonatal rat constitutes a lower percentage of the total GPAT activity than in the adult. We postulate that GPAT expression is modulated uniquely in each tissue according to specific needs for triacylglycerol storage. (C) 2001 Elsevier Science.