Introduction Besides its orexigenic nature in the hypothalamus (Zarjevski et al. 1993, Yang et al. 2009, Sousa-Ferreira et al. 2011), neuropeptide Y (NPY) induces obesity and metabolic alterations independent of hyperphagia. In humans, a
Liisa Ailanen, Suvi T Ruohonen, Laura H Vähätalo, Katja Tuomainen, Kim Eerola, Henriikka Salomäki-Myftari, Matias Röyttä, Asta Laiho, Markku Ahotupa, Helena Gylling, and Eriika Savontaus
Mathias V Schmidt, Claudia Liebl, Vera Sterlemann, Karin Ganea, Jakob Hartmann, Daniela Harbich, Stephanie Alam, and Marianne B Müller
able to ameliorate the initial HPA axis activation due to maternal separation by glucose replacement or by antagonizing the growth hormone (GH) secretagogue receptor (i.e. ghrelin receptor). Based on these data we hypothesized that neuropeptide Y (NPY
Susannah Cleary, Jacqueline K Phillips, Thanh-Truc Huynh, Karel Pacak, Abdel G Elkahloun, Jennifer Barb, Robert A Worrell, David S Goldstein, and Graeme Eisenhofer
proteins and peptides that are stored and processed within chromaffin granules from where they are coreleased with catecholamines, thereby potentially contributing to the clinical manifestations of these tumours ( Parmer & Zinder 2002 ). Neuropeptide Y
Kikuko Hotta, Masahiro Hosaka, Atsushi Tanabe, and Toshiyuki Takeuchi
-concentrating hormone (MCH), neuropeptide Y (NPY), and POMC in the hypothalamus, and it forms granule-like structures in association with these neuropeptides ( Tanabe et al . 2007 ). Furthermore, SCG3 is known to bind chromogranin A (CGA) and targets it to the
E Guillod-Maximin, A F Roy, C M Vacher, A Aubourg, V Bailleux, A Lorsignol, L Pénicaud, M Parquet, and M Taouis
intake such as the arcuate nucleus. Using, homozygous transgenic pro-opiomelanocortin (POMC) and neuropeptide Y (NPY)-green fluorescent protein (GFP) mice we demonstrate the expression of Adipor1/Adipor2 in POMC and NPY neurons. Finally, we show that
J P H Wilding, M O Ajala, P D Lambert, and S R Bloom
Neuropeptide Y (NPY) is the most powerful appetite stimulant known, and rates of synthesis and release in the hypothalamus correlate closely with nutritional status. Pregnancy and lactation provide an excellent model of physiological hyperphagia. In this study the authors measured food intake, plasma glucose, insulin and luteinizing hormone (LH) and hypothalamic NPY mRNA in rats during pregnancy and in early and late lactation. The effect of food restriction (to 80% of control) during lactation was also studied. Pregnancy resulted in a modest increase in daily food intake over non-lactating controls (controls: 15·6±0·6 g, pregnant: 19·8±1·1 g, P<0·01) During lactation food intake increased dramatically to 355% of non-lactating levels by the 12th day. Insulin and glucose levels were unchanged in lactation, except in the food-restricted animals, when insulin levels were reduced to 49·5±18·4 pmol/l compared with 215±55 pmol/l (P<0·01) in lactating, non-restricted animals, and glucose was reduced to 3·7±0·2 mmol/l compared with 5·1 ± 0·2 mmol/l in non-restricted lactating animals. Hypothalamic NPY mRNA was unchanged in pregnancy, moderately increased after 5 days lactation (130±6·2% of control, P<0·01) and increased further at 14 days lactation (179 ± 14%, P<0·001). The greatest changes occurred in the animals who were food-deprived during lactation, when hypothalamic NPY mRNA levels reached 324 ± 44% (P<0·001) of non-lactating levels. Increases in hypothalamic NPY synthesis may be partly responsible for the increase in food intake seen in lactation, but unlike in food deprivation, the increase is not related to circulating insulin, suggesting involvement of other regulatory factors.
Journal of Endocrinology (1997) 152, 365–369
CD McMahon, DF Buxton, TH Elsasser, DR Gunter, LG Sanders, BP Steele, and JL Sartin
The objective of this study was to determine whether neuropeptide Y (NPY) and recombinant human interleukin-1 receptor antagonist (IL-1ra) would: first, increase food intake; secondly, decrease concentrations of GH; thirdly, reduce GHRH-induced release of GH; and fourthly, reduce changes to concentrations of IGF-I in plasma during experimental endotoxemia in sheep. Six treatments were given to six castrated male sheep in a 6x6 Latin square treatment order. Osmotic mini-pumps were implanted at 0 h and a jugular vein was cannulated. Each sheep was continuously infused with saline (0.9%) or lipopolysaccharide (LPS) (20 micrograms/kg per 24 h, s.c.) at 10 microliters/h for 72 h via the osmotic mini-pumps. Blood samples (3 ml) were collected at 15-min intervals from 24 to 33 h. At 26 h, one of three treatments (artificial cerebrospinal fluid, NPY or IL-1ra) was injected i.c.v. within 30 s (0.3 microgram/kg), then infused i.c.v. from 26 to 33 h (600 microliters/h) at 0.3 microgram/kg per h. GHRH was injected i.v. (0.075 microgram/kg) at 32 h after which blood samples were collected at 5, 10, 15, 30, 45 and 60 min. Feed intake was reduced up to 50% for 48 h in LPS-treated compared with non-LPS-treated sheep. NPY restored feed intake in LPS-treated sheep and induced hyperphagia in non-LPS-treated sheep from 24 to 48 h. In contrast, IL-1ra did not affect appetite. Injection of NPY increased concentrations of GH from 26 to 27 h, while IL-1ra had no effect. Infusion of NPY suppressed GHRH-induced release of GH. However, no treatment altered pulse secretion parameters of GH. Concentrations of IGF-I were 20% higher at 72 h in LPS-treated sheep given NPY than in sheep treated with LPS alone, and this may reflect increased appetite from 24 to 48 h. We concluded that reduced appetite during endotoxemia is due to down-regulation of an NPY-mediated mechanism. Furthermore, NPY stimulates release of GH in healthy sheep, does not reduce pulse secretion parameters of GH, but does suppress GHRH-induced release of GH in endotoxic sheep. Therefore, NPY may be an important neurotransmitter linking appetite with regulation of GH during endotoxemic and healthy states in sheep.
Rodolfo C Cardoso, Bruna R C Alves, Ligia D Prezotto, Jennifer F Thorson, Luis O Tedeschi, Duane H Keisler, Marcel Amstalden, and Gary L Williams
), leptin's influence on the metabolic control of reproductive maturation is probably relayed by intermediate pathways. Neuropeptide Y (NPY) neurons in the arcuate nucleus (ARC) contain the leptin receptor ( Baskin et al . 1999 ), play an orexigenic role in
Luba Sominsky, Ilvana Ziko, Thai-Xinh Nguyen, Julie Quach, and Sarah J Spencer
amphetamine-regulated transcript (CART) neurons. Simultaneously, leptin inhibits the orexigenic neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons, thus suppressing feeding ( Cowley et al . 2001 ). In obesity, excess adiposity and hence
M Tang-Christensen, P Kristensen, CE Stidsen, CL Brand, and PJ Larsen
A number of neuropeptide Y (NPY) receptor subtypes, including the recently cloned Y5 receptor, have been implicated in the stimulation of food intake. In the present study, Y5 receptor antisense oligodeoxynucleotides (ODNs) were used to assess the potential involvement of the Y5 receptor in the regulation of spontaneous as well as NPY-induced food intake. Repeated central administration of Y5 antisense ODN significantly decreased spontaneous food intake and subsequently resulted in a significant weight loss. Furthermore, Y5 antisense ODN pre-treatment significantly inhibited the robust feeding response elicited by central administration of NPY (5.3+/-0. 8 vs 1.08+/-0.28 g, vehicle+/-s.e.m. vs Y5 ODN+/-s.e.m.). The present results provide evidence that central Y5 receptors are involved in both spontaneous as well as NPY-induced food intake, which may prove to be a new therapeutic route in the treatment of obesity and other disorders of appetite.