高脂肥胖大鼠血清瘦素,胰岛素及下丘脑细胞因子信号转导抑制因子-3基因表达的研究

目的观察高脂饮食肥胖大鼠血清瘦素,胰岛素水平及下丘脑细胞因子信号转导抑制因子-3基因(suppressors-of-cytokine-signaling 3,SOCS-3)表达变化及其关系,探讨高脂饮食肥胖大鼠引发瘦素抵抗及胰岛素抵抗的发生机制。方法以高脂饮食制备幼年雄性肥胖大鼠模型,采用放射免疫法检测各组大鼠血清瘦素、胰岛素及C肽浓度,葡萄糖氧化酶法检测血清葡萄糖水平,利用RT-PCR技术检测各组大鼠下丘脑SOCS-3基因表达水平。结果 (1)高脂饮食诱导的肥胖组大鼠体重明显高于对照组;(2)肥胖组大鼠血清瘦素、胰岛素,血糖及C肽水平明显升高,与对照组比较均有显著性差异;(3)肥胖组大鼠下丘脑SOCS-3的mRNA水平明显高于对照组;(4)肥胖组大鼠下丘脑内SOCS-3 mRNA水平分别与血清瘦素、胰岛素含量呈显著正相关。结论高脂饮食诱导的肥胖大鼠可出现瘦素抵抗和胰岛素抵抗以及SOCS-3基因表达上调。SOCS-3基因表达上调使瘦素及胰岛素受体后JAK-STAT信号转导通路抑制,可能参与了瘦素及胰岛素抵抗的发生机制。

CHANGES OF SERUM LEPTIN SERUM INSULIN AND SUPPRESSORS OF CYTOKINE SIGNALING-3 GENE EXPRESSION IN HYPOTHALAMUS OF OBESE RATS FED HIGH-FAT DIET

Objective To observe the concentration of serum leptin,serum insulin and changes of suppressorsof-cytokine-signaling 3(SOCS-3) gene expression in hypothalamus of obese rats fed with high-fat diet,and to explore the pathogenesis of leptin resistance and insulin resistance.Method Four-week-old healthy male SD rats were fed with high-fat diet to set up the animal model of dietary obesity.The concentration of serum leptin,serum insulin and C peptide was measured with radioimmunoassay.The concentration of glucose was measured with glucose oxidase method.Expression of SOCS-3 mRNA in the hypothalamus was detected with semiquantitative RT-PCR.Results(1) The body weight of rats fed high-fat diet was increased significantly than that in control group;(2) The concentration of serum leptin,insulin,glucose and C peptide in rats of obese group was elevated obviously compared with control group;(3) The expression of SOCS-3mRNA in obese group was increased markedly compared with control group;(4) There were significant positive relationship between SOCS-3 mRNA expression in hypothalamus and serum leptin,insulin concentration in obese group.Conclusion High-fat diet can lead to leptin resistance,insulin resistance and upregulation of SOCS-3 expression,which may act as the negative factors of JAK/STAT pathway that result in leptin resistance and insulin resistance in obese rats.