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Analysis of hypothalamic transcripts induced by leptin

瘦素诱导的下丘脑转录本分析

基本信息

批准号：
13680849
负责人：
MORIKAWA Yoshihiro
金额：
$ 0.77万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680849/
关键词：
leptin neuron insulin receptor subtraction phosphorylation transcription factor MAP kinase MAP Kinase

项目摘要

Leptin receptor is essential for mediating the effects of leptin on mammalian body weight homeostasis. However, the range of transcriptional targets responsive to leptin receptor activation, and the likely mediators of leptin action remain unclear. We have used PCR-Select cDNA subtraction to identify transcripts induced by leptin in the hypothalamus of murine brain. Differential expression of the identified transcripts in the hypothalamus was confirmed by Northern blotting. In situ hybridization studies indicate that these transcripts were expressed in the mouse central nervous system. Comparative analysis of hypothalamic *lices generated from control and leptin-injected ob/ob mice demonstrated that a subset of the identified transcripts was induced after leptin injection.Fasting for 48h induced the phosphorylation of ERK1/2 in the hypothalamic arcuate (ARC) and paraventricular nuclei (PVN) of mice. Phosphorylation of p38 was increased in the paraventricular nucleus, whereas phosphorylation of JNK was not detected. In ob/ob mice, hyperphosphorylation of ERK1/2 in ARC and PVN was observed, which was down-regulated by fasting. In addition, a novel role of STAT5 in adipocyte differentiation was observed, and we are analyzing in the hypothalamus of mice expressed dn-STAT5A in an adipose tissue-specific fashion.

瘦素受体在介导瘦素对哺乳动物体重动态平衡的影响中起重要作用。然而，对瘦素受体激活作出反应的转录靶点的范围，以及可能的瘦素作用的介体仍不清楚。我们用PCR-Select cDNA差减技术鉴定了瘦素在小鼠大脑下丘脑中诱导的转录产物。Northern印迹分析证实，鉴定出的转录本在下丘脑中的表达存在差异。原位杂交研究表明，这些转录本在小鼠中枢神经系统中表达。对对照和注射瘦素的ob/ob小鼠下丘脑切片的对比分析表明，注射瘦素后诱导了已鉴定的转录子的一部分。禁食48h诱导了小鼠下丘脑弓状核(ARC)和室旁核(PVN)ERK1/2的磷酸化。室旁核中p38的磷酸化增加，而JNK的磷酸化未检测到。在ob/ob小鼠中，观察到ERK1/2在ARC和PVN中过度磷酸化，并被禁食下调。此外，还观察到了STAT5在脂肪细胞分化中的新作用，我们正在分析以脂肪组织特异性方式在小鼠下丘脑中表达的DN-STAT5A。