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This version published online on April 6, 2006
Endocrinology, doi:10.1210/en.2005-0877
A more recent version of this article appeared on July 1, 2006
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Submitted on July 13, 2005
Accepted on March 29, 2006

Characterization of leptin responsive neurons in the caudal brainstem

Kate L.J. Ellacott, Ilia G. Halatchev, and Roger D. Cone*

Center for the Study of Weight Regulation and Associated Disorders and Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, Phone: (503) 494-4668, Fax: (503) 494-5235, E-mail: cone@ohsu.edu

* To whom correspondence should be addressed. E-mail: cone{at}ohsu.edu.

The central melanocortin system plays a key role in the regulation of energy homeostasis. Neurons containing the peptide precursor pro-opiomelanocortin (POMC) are found at two sites in the brain, the arcuate nucleus of the hypothalamus (ARC) and the caudal region of the nucleus of the solitary tract (NTS). ARC POMC neurons, which also express cocaine and amphetamine regulated transcript (CART), are known to mediate part of the response to factors regulating energy homeostasis, such as leptin and ghrelin. In contrast, the physiological role(s) of the POMC neurons in the caudal brain stem are not well characterized. However, development of a transgenic mouse expressing green fluorescent protein under the control of the POMC promoter (POMC-EGFP mouse) has aided the study of these neurons. Indeed, recent studies have shown significant activation of NTS POMC-EGFP cells by the gut released satiety factor cholecystokinin (CCK). Here we show that peripheral leptin administration induces the expression of phospho-signal transducer and activator of transcription 3 immunoreactivity (pSTAT3-IR), a marker of leptin receptor signaling, in > 50% of NTS POMC-EGFP neurons. Furthermore, these POMC-EGFP neurons comprise 30% of all pSTAT3-IR cells in the NTS. Additionally, we also show that in contrast to the ARC population, NTS POMC-EGFP neurons do not co-express CART immunoreactivity. This data suggests that NTS POMC neurons may participate with ARC POMC cells in mediating some of the effects of leptin, and thus comprise a novel cell group regulated by both long-term adipostatic signals, as well as satiety factors such as CCK.
Key words: Pro-opiomelanocortin (POMC) • leptin • nucleus of the tractus solitarius (NTS) STAT-3 • melanocortin • caudal brainstem




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