Analysis of hypothalamic transcripts induced by leptin

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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.