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Compared with diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y\/agouti-related peptide (NPY\/AgRP) and \u03b1-melanocyte-stimulating hormone (\u03b1-MSH; from proopiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC but not NPY\/AgRP neurons. Since amylin increases leptin signaling in adult rats, we treated DIO neonates with amylin during postnatal hypothalamic development and assessed leptin signaling, leptin-dependent ARC-PVN pathway development, and metabolic changes. DIO neonates treated with amylin from P0\u20136 and from P0\u201316 increased ARC leptin signaling and both AgRP and \u03b1-MSH ARC-PVN pathway development, but increased only POMC neuron number. Despite ARC-PVN pathway correction, P0\u201316 amylin-induced reductions in body weight did not persist beyond treatment cessation. Since amylin enhances adult DIO ARC signaling via an IL-6-dependent mechanism, we assessed ARC-PVN pathway competency in IL-6 knockout mice and found that the AgRP, but not the \u03b1-MSH, ARC-PVN pathway was reduced. These results suggest that both leptin and amylin are important neurotrophic factors for the postnatal development of the ARC-PVN pathway. Amylin might act as a direct neurotrophic factor in DIO rats to enhance both the number of POMC neurons and their \u03b1-MSH ARC-PVN pathway development. This suggests important and selective roles for amylin during ARC hypothalamic development.<\/jats:p>","DOI":"10.1152\/ajpregu.00326.2016","type":"journal-article","created":{"date-parts":[[2016,9,15]],"date-time":"2016-09-15T03:08:40Z","timestamp":1473908920000},"page":"R1032-R1044","source":"Crossref","is-referenced-by-count":35,"title":["Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred diet-induced obese rat"],"prefix":"10.1152","volume":"311","author":[{"given":"Miranda D.","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien G.","family":"Bouret","sequence":"additional","affiliation":[{"name":"The Saban Research Institute, Developmental Neuroscience Program, Children's Hospital Los Angeles, University of Southern 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