Institute of Nutrition, China Medical University, Taichung, Taiwan, ROC.
Ann Nutr Metab. 2010;57(3-4):169-76. doi: 10.1159/000321966. Epub 2010 Nov 16.
Establishing animal models with metabolic disorders similar to human metabolic syndrome (MS) is important. In terms of eliciting a full array of MS, we have previously shown that Wistar rats are more responsive to sucrose water drinking than are C57BL/6J mice. This study was aimed at investigating the underlying molecular mechanism of sucrose water-induced MS in Wistar rats.
Male Wistar rats were divided into 2 groups (n = 8 for each group) which were given plain water (C group) or 30% sucrose water (SW group) to drink ad libitum. After 20 weeks, the transcriptional levels and protein translocation of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate response element-binding protein (ChREBP) as well as the protein levels of protein tyrosine phosphatase-1B (PTP-1B) in insulin-responsive tissues (liver, muscle, and adipose tissue) were measured.
The sucrose water regimen successfully elicited visceral obesity, hypertriglyceridemia, insulin resistance, and high blood pressure. The upregulation of de novo lipogenesis in the liver of the sucrose water-treated rats was demonstrated by an increased activity of enzymes, mRNA levels of lipogenic proteins, and nuclear levels of SREBP-1c and ChREBP. Moreover, in the sucrose water-treated rats, protein levels of PTP-1B were significantly increased in liver and skeletal muscle but decreased in adipose tissue.
The susceptibility of Wistar rats to sucrose water-induced MS is associated with the transactivation of SREBP-1c and ChREBP in the liver, and PTP-1B is involved in the upregulation of de novo lipogenesis in the liver and the pathology of systemic insulin resistance in rats with MS chronically induced by drinking sucrose water.
建立与人类代谢综合征(MS)相似的代谢紊乱动物模型非常重要。就诱发 MS 的全套表现而言,我们之前已经表明,Wistar 大鼠对蔗糖水的反应比 C57BL/6J 小鼠更为敏感。本研究旨在探讨 Wistar 大鼠蔗糖水诱导 MS 的潜在分子机制。
雄性 Wistar 大鼠分为两组(每组 8 只),分别给予普通水(C 组)或 30%蔗糖水(SW 组)自由饮用。20 周后,测量肝脏固醇调节元件结合蛋白-1c(SREBP-1c)和碳水化合物反应元件结合蛋白(ChREBP)的肝转录水平和蛋白易位,以及胰岛素反应组织(肝脏、肌肉和脂肪组织)中蛋白酪氨酸磷酸酶-1B(PTP-1B)的蛋白水平。
蔗糖水方案成功诱发内脏肥胖、高甘油三酯血症、胰岛素抵抗和高血压。蔗糖水治疗大鼠肝脏中新生脂肪生成的上调通过酶活性、脂生成蛋白的 mRNA 水平以及 SREBP-1c 和 ChREBP 的核水平得到证实。此外,在蔗糖水治疗的大鼠中,肝脏和骨骼肌中的 PTP-1B 蛋白水平显著增加,而脂肪组织中的 PTP-1B 蛋白水平则降低。
Wistar 大鼠对蔗糖水诱导的 MS 的易感性与肝脏中 SREBP-1c 和 ChREBP 的转激活有关,而 PTP-1B 参与了蔗糖水诱导的 MS 大鼠肝脏中新生脂肪生成的上调和全身胰岛素抵抗的病理过程。