Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Pediatr Res. 2013 Mar;73(3):263-7. doi: 10.1038/pr.2012.190. Epub 2012 Dec 10.
Suppressor of cytokine signaling-1 and -3 (SOCS-1 and SOCS-3) are two important negative regulators in the insulin-signaling pathway, and their overexpression may aggravate insulin resistance. Subjects with insulin resistance are often obese and have increased expressions of SOCS-1 and SOCS-3. We speculated that SOCS-1 and SOCS-3 may be involved in abnormal deposition of adipose tissues during insulin resistance.
A catch-up growth intrauterine growth retardation (CG-IUGR) rat model with insulin resistance was established; mRNA and protein expression of SOCS-1, SOCS-3, the CCAAT/enhancer binding protein (C/EBPα), and peroxisome proliferator-activated receptor (PPARγ) in adipose tissue were measured by real-time PCR and western blot; plasmids carrying small hairpin RNAs (shRNAs) targeting the SOCS-1 and SOCS-3 genes were constructed and transfected into preadipocytes, which were then induced to mature. At 72 h after differentiation was induced, the expressions of C/EBPα and PPARγ, two important molecules promoting the differentiation of preadipocytes, were detected.
Expressions of SOCS-1, SOCS-3, C/EBPα, and PPARγ were markedly increased in adipose tissues of CG-IUGR rats, whereas the expressions of C/EBPα and PPARγ were significantly reduced after gene silencing of SOCS-1 or SOCS-3 in adipocytes.
Overexpression of SOCS-1 and SOCS-3 may enhance the expression of C/EBPα and PPARγ, resulting in abnormal deposition of adipose tissues during insulin resistance.
细胞因子信号转导抑制因子-1 和 -3(SOCS-1 和 SOCS-3)是胰岛素信号通路中的两个重要负调控因子,其过度表达可能加重胰岛素抵抗。胰岛素抵抗患者常肥胖,SOCS-1 和 SOCS-3 表达增加。我们推测 SOCS-1 和 SOCS-3 可能参与胰岛素抵抗时脂肪组织的异常沉积。
建立胰岛素抵抗追赶生长宫内发育迟缓(CG-IUGR)大鼠模型;实时 PCR 和 Western blot 检测脂肪组织中 SOCS-1、SOCS-3、CCAAT/增强子结合蛋白(C/EBPα)和过氧化物酶体增殖物激活受体(PPARγ)的 mRNA 和蛋白表达;构建针对 SOCS-1 和 SOCS-3 基因的短发夹 RNA(shRNA)质粒,并转染人前脂肪细胞,诱导其成熟。分化诱导 72 h 后,检测促进前脂肪细胞分化的两个重要分子 C/EBPα 和 PPARγ 的表达。
CG-IUGR 大鼠脂肪组织中 SOCS-1、SOCS-3、C/EBPα 和 PPARγ 的表达明显增加,而 SOCS-1 或 SOCS-3 基因沉默后脂肪细胞中 C/EBPα 和 PPARγ 的表达明显降低。
SOCS-1 和 SOCS-3 的过度表达可能增强 C/EBPα 和 PPARγ 的表达,导致胰岛素抵抗时脂肪组织的异常沉积。