Analysis of hypothalamic transcripts induced by leptin

瘦素受体是介导瘦素对哺乳动物体重稳态影响的关键。然而，瘦素受体激活的转录靶点的范围，以及瘦素作用的可能介质仍不清楚。我们已经使用PCR-Select cDNA减法来鉴定小鼠脑下丘脑中瘦素诱导的转录物。通过北方印迹证实了下丘脑中鉴定的转录物的差异表达。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。对对照组和注射瘦素的ob/ob小鼠下丘脑 * 切片的比较分析表明，瘦素诱导了一部分已鉴定的转录本，禁食48 h诱导了小鼠下丘脑弓状核和室旁核ERK 1/2的磷酸化。室旁核p38磷酸化增加，而JNK磷酸化未检测到。在ob/ob小鼠中，观察到ARC和PVN中ERK 1/2的过度磷酸化，其被禁食下调。此外，观察到STAT 5在脂肪细胞分化中的新作用，我们正在分析小鼠下丘脑中以脂肪组织特异性方式表达的dn-STAT 5A。

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.