Rahmouni Kamal, Mark Allyn L, Haynes William G, Sigmund Curt D
Hypertension Genetics Specialized Center of Research, Cardiovascular Center, Department of Internal Medical, University of Iowa Carver College of Medicine, Iowa City 52242, USA.
Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E891-5. doi: 10.1152/ajpendo.00551.2003. Epub 2004 Jan 28.
Adipose tissue represents an important source of angiotensinogen (AGT). We investigated the effect of obesity induced by a high-fat diet on the expression of mouse (mAGT) and human AGT (hAGT) genes in liver, kidney, and heart and different adipose depots in normal mice (C57BL/6J), and in transgenic mice expressing the hAGT gene under the control of its own promoter. Mice were fed a high-fat diet (45% kcal) or normal chow (10% kcal) for 10 and 20 wk. The expression of mAGT and hAGT mRNA was quantified using an RNAse protection assay. Mice on the high-fat diet exhibited increased weight, fat mass, and plasma leptin. Expression of mAGT or hAGT genes was not affected by high-fat diet in nonadipose tissues, brown adipose tissue, or subcutaneous white fat. In contrast, high-fat diet increased both mAGT and hAGT gene expression in visceral adipose depots (omental, reproductive, and perirenal fat). Thus obesity-induced by a high-fat diet is associated with a tissue-specific increased expression of both mouse and human AGT genes in intra-abdominal adipose tissue. Our findings also suggest that 1.2 kb of regulatory sequences present in the hAGT transgene are sufficient to transcriptionally respond to a high-fat diet in an adipose-specific and depot-specific manner.
脂肪组织是血管紧张素原（AGT）的重要来源。我们研究了高脂饮食诱导的肥胖对正常小鼠（C57BL/6J）以及在其自身启动子控制下表达人AGT（hAGT）基因的转基因小鼠的肝脏、肾脏、心脏和不同脂肪库中小鼠（mAGT）和人AGT（hAGT）基因表达的影响。小鼠分别喂食高脂饮食（45%千卡）或正常饲料（10%千卡）10周和20周。使用核糖核酸酶保护分析法对mAGT和hAGT mRNA的表达进行定量。高脂饮食的小鼠体重、脂肪量和血浆瘦素增加。非脂肪组织、棕色脂肪组织或皮下白色脂肪中的mAGT或hAGT基因表达不受高脂饮食影响。相反，高脂饮食增加了内脏脂肪库（网膜、生殖和肾周脂肪）中mAGT和hAGT基因的表达。因此，高脂饮食诱导的肥胖与腹内脂肪组织中小鼠和人AGT基因的组织特异性表达增加有关。我们的研究结果还表明，hAGT转基因中存在的1.2 kb调控序列足以以脂肪特异性和库特异性方式对高脂饮食做出转录反应。
