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SOCS1/3 基因沉默对大鼠前体脂肪细胞分化成熟过程中 C/EBPα 和 PPARγ 表达的影响。

Effects of SOCS 1/3 gene silencing on the expression of C/EBPα and PPARγ during differentiation and maturation of rat preadipocytes.

机构信息

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Pediatr Res. 2013 Mar;73(3):263-7. doi: 10.1038/pr.2012.190. Epub 2012 Dec 10.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

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