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Title: Moderate long-term modulation of neuropeptide Y in hypothalamic arcuate nucleus induces energy balance alterations in adult rats
Authors: Sousa-Ferreira, Lígia 
Garrido, Manuel Joaquim Marques 
Nascimento-Ferreira, Isabel 
Nóbrega, Clévio 
Carvalho, Ana dos Santos 
Álvaro, Ana Rita Costa Silva 
Salgado, Joana Rosmaninho 
Kaster, Manuella
Kügler, Sebastian 
Almeida, Luís Pereira de 
Cavadas, Cláudia 
Issue Date: 2011
Publisher: Public Library of Science
Project: This work was supported by the Portuguese Foundation for Science and Technology, FEDER and COMPETE [PTDC/SAU-FCF/099082/2008; PTDC/SAUFCF/ 70384/2006; PTDC/SAU/NEU/73119/2006; SFRH/BD/30608/2006; SFRH/BD/29479/2006; SFRH/BPD/62945/2009; SFRH/BD/45311/2008, SFRH/BPD/49079/2008; SFRH/BPD/46086/2008; SFRH/BPD/31547/2006] 
Serial title, monograph or event: PLoS ONE
Volume: 6
Issue: 7
Abstract: Neuropeptide Y (NPY) produced by arcuate nucleus (ARC) neurons has a strong orexigenic effect on target neurons. Hypothalamic NPY levels undergo wide-ranging oscillations during the circadian cycle and in response to fasting and peripheral hormones (from 0.25 to 10-fold change). The aim of the present study was to evaluate the impact of a moderate long-term modulation of NPY within the ARC neurons on food consumption, body weight gain and hypothalamic neuropeptides. We achieved a physiological overexpression (3.6-fold increase) and down-regulation (0.5-fold decrease) of NPY in the rat ARC by injection of AAV vectors expressing NPY and synthetic microRNA that target the NPY, respectively. Our work shows that a moderate overexpression of NPY was sufficient to induce diurnal over-feeding, sustained body weight gain and severe obesity in adult rats. Additionally, the circulating levels of leptin were elevated but the immunoreactivity (ir) of ARC neuropeptides was not in accordance (POMC-ir was unchanged and AGRP-ir increased), suggesting a disruption in the ability of ARC neurons to response to peripheral metabolic alterations. Furthermore, a dysfunction in adipocytes phenotype was observed in these obese rats. In addition, moderate down-regulation of NPY did not affect basal feeding or normal body weight gain but the response to food deprivation was compromised since fasting-induced hyperphagia was inhibited and fasting-induced decrease in locomotor activity was absent.These results highlight the importance of the physiological ARC NPY levels oscillations on feeding regulation, fasting response and body weight preservation, and are important for the design of therapeutic interventions for obesity that include the NPY.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0022333
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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