Identification of leptin-induced transcripts in the mouse hypothalamus

Long-form leptin receptor (OB-R-L) is a signal-transducing member of the cy tokine receptor superfamily that is essential for mediating the effects of leptin on mammalian body weight homeostasis. At present, the range of trans criptional targets responsive to OB-R-L activation, and consequently, the l ikely mediators of leptin action, remain undefined. In this report, we have used cDNA subtractive hybridization to identify transcripts induced by lep tin in immortalized hypothalamic neurons expressing OB-R-L. Differential ex pression of the identified transcripts in these cells was confirmed by both array technology and Northern blotting. In situ hybridization studies indi cate that these transcripts are expressed in the mouse central nervous syst em, including nuclei of the hypothalamus that coexpress OB-R-L. Comparative in situ analysis of slices of hypothalami generated from control and lepti n-injected ob/ob mice demonstrates that a subset of the identified transcri pts is induced in vivo after leptin injection. The potential role of the pr oteins encoded by these transcripts Tn mediating the effects of leptin on b ody weight and energy homeostasis are discussed.