Neuropeptide Y Concentrations Research Articles

Neuropeptide Y and dipeptidyl peptidase IV in normally cycling and postmenopausal women: A prospective pilot study.

The purpose was to investigate changes in neuropeptide Y (NPY) protein and dipeptidyl peptidase IV (DPP-IV) activity in the plasma and saliva in normally cycling women and women after menopause. We recruited 7 cycling women and 7 postmenopausal women for a cross-sectional, prospective pilot study. Blood via venipuncture and saliva samples were taken at each point in the menstrual cycle (premenopausal) or once per week (postmenopausal) for 2 months. Blood and saliva were analyzed for estrogen, NPY using ELISA and DPP-IV activity using a fluorometric assay. Plasma β-estradiol was an average of 96.45 ± 57.04 pg/mL over 2 cycles in the premenopausal group and 1.72 ± 0.35 pg/mL over 2 months in the postmenopausal group (P < .05). In the cycling group, there were no significant differences in saliva or plasma NPY or DPP-IV over the cycle. For the postmenopausal group, salivary NPY and DPP-IV did not change over 2 months. Plasma NPY was lowest in the middle 2 weeks (average: 0.52 ± 0.10 ng/mL) compared to the first and fourth weeks (average of week 1 and 4: 0.60 ± 0.14 ng/mL; P < .05). Plasma NPY in postmenopausal women was higher overall (0.56 ± 0.13 ng/mL) compared to cycling women (0.30 ± 0.11 ng/mL; P < .05). Plasma DPP-IV activity was unchanged by time in the postmenopausal group. Saliva DPP-IV and saliva NPY in the cycling group had a significant negative correlation (R = −0.95; P < .05). We found that saliva measures of NPY and DPP-IV activity appear to be poor estimates of plasma concentrations and activities, but a larger sample size is required to conform this. Differences in plasma NPY concentrations between the groups and the relationship between salivary NPY and DPP-IV suggests that there may be some unique differences between these groups.

Association between adiposity and fasting serum levels of appetite-regulating peptides: Leptin, neuropeptide Y, desacyl ghrelin, peptide YY(1-36), obestatin, cocaine and amphetamine-regulated transcript, and agouti-related protein in nonobese participants

The objective of this study was to evaluate the association between adiposity parameters and fasting serum levels of appetite-regulating peptides: leptin, neuropeptide Y (NPY), desacyl ghrelin, peptide YY(1-36), obestatin, cocaine- and amphetamine-regulated transcript (CART), and agouti-related protein in 30 healthy, non-obese subjects. Thirty European Caucasian adult participants were included in the study (17 men and 13 women). Body composition (body fat and lean body mass) was determined using bioelectrical impedance analysis. Concentrations of peptides in serum were assessed using the enzyme-linked immunosorbent assay. Women had higher level of leptin (P < 0.001), with no other differences for analyzed peptides. We have found a significant correlation between serum concentrations of CART and NPY (P < 0.001). Fasting leptin level was associated with age (P = 0.002), waist circumference (P < 0.001), and lean body mass (P < 0.001). Levels of ghrelin were lower in participants with dyslipidemia (P = 0.009). Levels of obestatin (P = 0.008) and leptin (P = 0.02) were higher in participants with insulin resistance. Associations between body fat and appetite-regulating peptides are more complex than simple feedback loops. Leptin is probably the first signal in the pathway that regulates body fat content, as of all analyzed peptides leptin was the only one that was associated with body composition or anthropometric measurements.

Neuropeptide Y receptor interactions regulate its mitogenic activity

Neuropeptide Y (NPY) is a multifunctional neurotransmitter acting via G protein-coupled receptors - Y1R, Y2R and Y5R. NPY activities, such as its proliferative effects, are mediated by multiple receptors, which have the ability to dimerize. However, the role of this receptor interplay in NPY functions remains unclear. The goal of the current study was to identify NPY receptor interactions, focusing on the ligand-binding fraction, and determine their impact on the mitogenic activity of the peptide. Y1R, Y2R and Y5R expressed in CHO-K1 cells formed homodimers detectable on the cell surface by cross-linking. Moreover, Y1R and Y5R heterodimerized, while no Y2R/Y5R heterodimers were detected. Nevertheless, Y5R failed to block internalization of its cognate receptor in both Y1R/Y5R and Y2R/Y5R transfectants, indicating Y5R transactivation upon stimulation of the co-expressed receptor. These receptor interactions correlated with an augmented mitogenic response to NPY. In Y1R/Y5R and Y2R/Y5R transfectants, the proliferative response started at picomolar NPY concentrations, while nanomolar concentrations were needed to trigger proliferation in cells transfected with single receptors. Thus, our data identify direct and indirect heterotypic NPY receptor interactions as the mechanism amplifying its activity. Understanding these processes is crucial for the design of treatments targeting the NPY system.

Somatostatin and Neuropeptide Y in Cerebrospinal Fluid: Correlations With Amyloid Peptides Aβ1-42 and Tau Proteins in Elderly Patients With Mild Cognitive Impairment.

A combination of low cerebrospinal fluid (CSF) Amyloid β1–42 (Aβ1–42) and high Total-Tau (T-Tau) and Phosphorylated-Tau (P-Tau) occurs at a prodromal stage of Alzheimer’s disease (AD) and recent findings suggest that network abnormalities and interneurons dysfunction contribute to cognitive deficits. Somatostatin (SOM) and Neuropeptide Y (NPY) are two neuropeptides which are expressed in GABAergic interneurons with different fates in AD the former only being markedly affected. The aim of this study was to analyze CSF SOM, NPY and CSF Aβ1–42; T-Tau, P-Tau relationships in 43 elderly mild cognitively impairment (MCI) participants from the Biomarker of AmyLoïd pepTide and AlZheimer’s disease Risk (BALTAZAR) cohort. In these samples, CSF SOM and CSF Aβ1–42 on the one hand, and CSF NPY and CSF T-Tau and P-Tau on the other hand are positively correlated. CSF SOM and NPY concentrations should be further investigated to determine if they can stand for early AD biomarkers.Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT01315639.

A17270 He neuroendocrine peculiarities of essential arterial hypertension development

Objectives: To investigate the potential role of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) in the pathogenesis of essential arterial hypertension (EAH). Methods: 25 patients with I-III stages of EAH and 14 practically healthy volunteers aged from 22 to 70 years were examined. The content of VIP and NPY in the blood plasma was determined by immuno-enzymatic methods using the Bachem Peninsula Laboratories, Inc. sets. Results: We found a significant initial decrease in the levels of NPY in the plasma of all the examined patients with EAH. Depending on stage of the disease, it was shown that as EAH progressed, the plasma NPY level decreased from 1,532 ± 0,386 ng/ml to 1,054 ± 0,148 ng/ml. Level of activity of NPY was found to be inversely proportional to the degree of BP increase. Consequently, a decrease in the level of NPY stipulates higher figures of BP in patients with EAH, contributing to the further progression of the disease. However, the activity of this neuropeptide in plasma of patients with stage II was comparable to that of healthy volunteers and was 0,843 ± 0,191 ng/ml, which was significantly higher than in patients with stage III (0,404 ± 0,043 ng/ml). That is, in the course of hypertension, compensatory normalization of VIP activity was observed at the stage of development of lesions of target organs, with the depletion of which irreversible disturbances of their function develop. The content of VIP in patients with “moderate” arterial hypertension (0,393 ± 0,057 ng/ml) was significantly lower than in healthy volunteers. Conclusion: We detected a dynamic decrease in the activity of NPY and VIP in patients with EAH which indicates the involvement of these regulatory peptides in the development of arterial hypertension.

Abstract 4147: Neuropeptide Y promotes osteolytic activity during bone invasion and metastasis in Ewing sarcoma

Abstract Ewing sarcoma (ES) is a pediatric malignancy affecting bones and soft tissues. The presence of metastases is associated with poor prognosis, particularly in patients with dissemination to the bone. ES cells produce and secrete high levels of neuropeptide Y (NPY), a 36-amino acid neurotransmitter normally released from peripheral sympathetic neurons, and express its receptors. Our previous studies in an ES xenograft model demonstrated that the severity of bone destruction in primary tumors and incidence of osseous metastases positively correlate with levels of NPY release and are significantly decreased with NPY shRNA. Thus, the goal of our study was to determine the mechanism of this NPY-induced osteolytic effect. Since tumor bone invasion and metastasis is associated with changes in osteolytic and osteogenic activity within bone, we assessed osteoblast and osteoclast content in bones adjacent to the ES xenografts. No significant difference in osteoblast number was observed between bones within ES xenografts with high and low NPY levels. However, TRAP assay showed that ES tumors secreting high NPY levels had significantly increased osteoclast density on the border of the bone-tumor interface, as compared to tumor tissues with minimal NPY secretion or treated with NPY shRNA. To identify the mechanisms underlying these osteolytic actions of NPY, we tested its effect on osteoclast recruitment and differentiation. Transwell migration assay showed that osteoclast precursors, RAW 264.7 murine macrophages, were recruited at significantly higher levels to the conditioned media from ES cells with high NPY release, as compared to those cells exposed to conditioned media from NPY-low ES cells. Similarly, ES-conditioned media with high NPY content had a higher ability to stimulate differentiation of RAW 264.7 cells into osteoclasts than those obtained from NPY-low ES cells. Both of these effects were exacerbated by hypoxic conditions, known to upregulate NPY and its Y5 receptors (Y5R) in ES cells. Blocking the expression of NPY and Y5R in ES cells with shRNA inhibited macrophage recruitment and osteoclastogenesis, and decreased RANKL content in conditioned media from NPY-high ES cells. Altogether, these data suggest that the NPY/Y5R autocrine loop stimulates the release of RANKL from ES cells, promoting macrophage recruitment and consequent osteoclast differentiation. Therefore, increased NPY secretion could have a significant impact on shifting bone homeostasis to promote osteolysis, bone invasion, and osseous metastasis. Further studies are needed to identify other factors released by tumor cells secreting high NPY levels and to test Y5R antagonists as a potential therapeutic option to inhibit these processes. Importantly, aside from ES, the above findings may be relevant to other NPY-rich tumors metastasizing to the bone, such as neuroblastoma. Citation Format: Richard Garner, Emily Hong, Shiya Zhu, Mina Adnani, Sung-Hyeok Hong, Susana Galli, Joanna Kitlinska. Neuropeptide Y promotes osteolytic activity during bone invasion and metastasis in Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4147.

Effects on cervical spondylosis of vertebral artery type and the concentrations of plasma NPY and UII in the patients treated with the modified acupuncture at unilateral/bilateral Renying (ST 9)

To observe the differences in the clinical therapeutic effects on cervical spondylosis of vertebral artery type (CSA) between the modified acupuncture and the routine acupuncture at unilateral/bilateral Renying (ST 9) as well as the impacts on the concentrations of plasma neuropeptide Y (NPY) and urotensinⅡ(UⅡ) in the patients. A total of 160 patients were divided into a modified bilateral acupuncture group, a modified unilateral acupuncture group, a routine bilateral acupuncture group and a routine unilateral acupuncture group, 40 cases in each one according to the random number table. In the modified bilateral acupuncture group, the modified acupuncture was applied bilaterally to Renying (ST 9). In the modified unilateral acupuncture group, the modified acupuncture was applied unilaterally to Renying (ST 9). In the routine bilateral acupuncture group, the routine acupuncture was applied bilaterally to Renying (ST 9). In the routine unilateral acupuncture group, the routine acupuncture was applied unilaterally to Renying (ST 9). The treatment was given once every day, continuously for 6 days as one course. Two courses of treatment were required at the interval of 1 day. In each group, before and after treatment, we observed the peak systolic blood flow velocity (Vs) of the vertebral artery (VA) and the basilar artery (BA), cervical vertigo symptoms and functional assessment scales (ESCV) and the concentration of plasma NPY and UⅡ. The clinical therapeutic effects were compared among the groups. After treatment, the clinical therapeutic effect in the modified bilateral acupuncture group was 90.0% (36/40), which was better than 80.0% (32/40) in the modified unilateral acupuncture group, 77.5% (35/40) in the routine bilateral acupuncture group and 65.0% (26/40) in the routine unilateral acupuncture group (all P<0.05). After treatment, Vs of VA and BA was improved remarkably in every group (all P<0.01), and the result in the modified bilateral acupuncture group was higher than those in the other groups (all P<0.01). After treatment, ESCV scores were all increased remarkably in every group (all P<0.01). ESCV score and improvement index in the modified bilateral acupuncture group were all higher than those in the other groups (P<0.05, P<0.01). After treatment, the concentrations of plasma NPY and UⅡ were all reduced remarkably in every group (all P<0.01) and the differences were significant among the groups (all P<0.01). The modified bilateral acupuncture at Renying (ST 9) effectively regulates the blood supply of the vertebral basilar artery and improves the cerebral circulation. The effects are superior to those of the unilateral acupuncture at Renying (ST 9).

Effects of Dietary Acute Tryptophan Depletion (ATD) on NPY Serum Levels in Healthy Adult Humans Whilst Controlling for Methionine Supply-A Pilot Study.

Central nervous serotonin (5-HT) can influence behaviour and neuropsychiatric disorders. Evidence from animal models suggest that lowered levels of neuropeptide Y (NPY) may have similar effects, although it is currently unknown whether decreased central nervous 5-HT impact NPY concentrations. Given that the production of NPY is dependent on the essential amino acid methionine (MET), it is imperative to account for the presence of MET in such investigations. Hence, this study sought to examine the effects of acute tryptophan depletion (ATD; a dietary procedure that temporarily lowers central nervous 5-HT synthesis) on serum concentrations of NPY, whilst using the potential renal acid load indicator (PRAL) to control for levels of MET. In a double-blind repeated measures design, 24 adult humans randomly received an AA-load lacking in TRP (ATD) on one occasion, and a balanced control mixture with TRP (BAL) on a second occasion, both with a PRAL of nearly 47.3 mEq of MET. Blood samples were obtained at 90, 180, and 240 min after each of the AA challenges. ATD, and therefore, diminished substrate availability for brain 5-HT synthesis did not lead to significant changes in serum NPY concentrations over time, compared to BAL, under an acute acidotic stimulus.

Circulating brain-derived neurotrophic factor, leptin, neuropeptide Y, and their clinical correlates in cystic fibrosis: a cross-sectional study.

IntroductionCystic fibrosis (CF) involves chronic inflammation and decreased pulmonary function, which increase caloric demand. Yet, sufficient energy provision is hindered by reduced appetite and fat malabsorption. Brain-derived neurotrophic factor (BDNF), leptin, and neuropeptide Y (NPY) belong to energy balance-regulating factors. We aimed to assess their concentrations in CF patients in order to search for potential clinical correlates.Material and methodsThis was an exploratory, cross-sectional study. Patients’ weight and height Z-scores, forced expiratory volume in 1 s (FEV1%), exocrine pancreatic status (fecal elastase-1), genotypes, and other characteristics were assessed. Serum concentrations of BDNF, leptin, NPY, IL-6, and TNF-α were measured using ELISA.ResultsThe study enrolled 56 patients, of whom 29 (52%) were female and 17 (30%) were younger than 16 years. Median (1st–3rd quartile) mass Z-score was –0.85 (–1.56–(–0.36)); median FEV1 was 70.5% (45.0–89.5); 48 (86%) patients had exocrine pancreatic insufficiency and 8 (14%) diabetes. Overall, median concentrations were: BDNF: 33.91 ng/ml (26.40–40.43), leptin: 12.05 ng/ml (8.93–17.77), NPY: 2.86 ng/ml (1.75–4.42). None of these factors correlated with mass Z-score, FEV1%, IL-6 or TNF-α. Leptin and NPY correlated negatively (ρ = –0.62, p = 3 × 10–7); BDNF/NPY ratio was associated with leptin (ρ = 0.54, p = 2 × 10–5), BDNF/leptin ratio correlated with NPY (ρ = 0.60, p = 1 × 10–6). In a multivariable regression analysis NPY was weakly, but independently, associated with FEV1%, and leptin with age.ConclusionsBDNF and leptin were not associated with weight Z-score or FEV1%. Serum NPY concentrations seemed to be lower in CF patients with reduced pulmonary function independently of malnutrition and inflammation.

Neuropeptide Y and Dipeptidyl Peptidase IV in Pre‐ and Post‐Menopausal Women

The purpose of this study was to investigate changes in neuropeptide Y (NPY) protein and dipeptidyl peptidase IV (DPP‐IV) activity in the plasma and saliva in normally cycling women and women after menopause. We recruited seven premenopausal women and seven post‐menopausal women for the study. Blood via venipuncture and saliva samples were taken at each point in the menstrual cycle (pre‐menopausal) or once per week (post‐menopausal) for 2 months. Blood and saliva were analyzed for estrogen, neuropeptide Y using ELISA's and DPP‐IV activity using a fluorometric assay. Plasma β‐estradiol was an average of 96.45±57.04 pg/ml over 2 cycles in the pre‐menopausal group and 1.72±0.35 pg/ml over 2 months in the post‐menopausal group (p&lt;0.05). In the pre‐menopausal group, there were no significant differences in saliva or plasma NPY or DPP‐IV over the cycle. For the post‐menopausal group, salivary NPY and DPP‐IV did not change over 2 months. Plasma NPY was lowest in the middle 2 weeks (average: 0.52±0.10 ng/ml) compared to the first and 4th weeks (average of week 1 and 4: 0.60±0.14 ng/ml; p&lt;0.05). Plasma NPY in postmenopausal women was higher overall (0.56±0.13 ng/ml) compared to pre‐menopausal women (0.30±0.11 ng/ml; p&lt;0.05). Plasma DPP‐IV activity was unchanged by time in the post‐menopausal group. Saliva DPP‐IV and saliva NPY in the pre‐menopausal group had a significant negative correlation (R=−0.95; p&lt;0.05). We found that saliva measures of NPY and DPP‐IV activity are poor estimates of plasma concentrations and activities. Differences in plasma NPY concentrations between the groups and the relationship between salivary NPY and DPP‐IV suggests that there are some unique differences between these groups.Support or Funding InformationThe work presented in this poster session was supported by Award Number 1R03DC013664‐01A1 from the National Institute on Deafness and Other Communication Disorders (NIDCD). The content of this presentation is solely the responsibility of the authors and does not necessarily represent the official views of the NIDCD or the National Institutes of Health.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Central Neuropeptide Y Plays an Important Role in Mediating the Adaptation Mechanism Against Chronic Stress in Male Rats.

Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF) and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days 1 through 5 of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, whereas central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, overexpressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress.

Effect of clozapine dose and concentration on fasting concentration of appetite regulating peptides

The aim of this study is to analyze whether clozapine serum concentration may affect fasting serum levels of several appetite regulating peptides: CART, PYY(1-36), NPY, AgRP, des-acylated ghrelin, leptin and obestatin. Serum concentration of clozapine and fasting serum levels of des-acylated ghrelin, neuropeptide Y (NPY), agouti-related protein (AgRP), peptide YY (PYY(1-36)), cocaine- and amphetamine-regulated transcript (CART), leptin and obestatin were measured in 30 subjects with schizophrenia on clozapine monotherapy. Leptin concentration was negatively correlated with clozapine dose (r = −0.53, p = 0.002), while NPY concentration was negatively correlated with clozapine concentration (r = −0.55, p = 0.01). Correlations with other peptides were not significant. We cannot conclude that serum concentration of clozapine is directly associated with increased or decreased level of appetite-regulating peptides.

Plasma Neuropeptide Y Levels in Vasovagal Syncope in Children.

Background:Vasovagal syncope (VVS) is the most common cause of syncope in children. Neuropeptide Y (NPY) plays an important role in the regulation of blood pressure (BP), as well as myocardial contractility. This study aimed to explore the role of plasma NPY in VVS in children.Methods:Fifty-six children who were diagnosed with VVS (VVS group) using head-up tilt test (HUT) and 31 healthy children who were selected as controls (control group) were enrolled. Plasma NPY concentrations were detected. The independent t-test was used to compare the data of the VVS group with those of the control group. The changes in plasma NPY levels in the VVS group during the HUT, as well as hemodynamic parameters, such as heart rate (HR), BP, total peripheral vascular resistance (TPVR), and cardiac output (CO), were evaluated using the paired t-test. Furthermore, the correlations between plasma NPY levels and hemodynamic parameters were analyzed using bivariate correlation analysis.Results:The BP, HR, and plasma NPY (0.34 ± 0.12 pg/ml vs. 0.46 ± 0.13 pg/ml) levels in the supine position were statistically low in the VVS group compared to levels in the control group (all P < 0.05). Plasma NPY levels were positively correlated with the HR (Pearson, R = 0.395, P < 0.001) and diastolic BP (Pearson, R = 0.311, P = 0.003) when patients were in the supine position. When patients in the VVS group were in the supine position, elevated TPVR (4.6 ± 3.7 mmHg·min−1·L−1 vs. 2.5 ± 1.0 mmHg·min−1·L−1, respectively, P < 0.001; 1 mmHg = 0.133 kPa) and reduced CO (1.0 ± 0.7 L/min vs. 2.4 ± 1.3 L/min, respectively, P < 0.001) were observed in the positive-response period compared with baseline values. The plasma NPY levels were positively correlated with TPVR (Spearman, R = 0.294, P = 0.028) but negatively correlated with CO in the positive-response period during HUT (Spearman, R = −0.318, P = 0.017).Conclusions:Plasma NPY may contribute to the pathogenesis of VVS by increasing the TPVR and decreasing the CO during orthostatic regulation.

Neuropeptide Y stimulates osteoblastic differentiation of murine MC3T3-E1 cells related to activated Wnt signaling in vitro

Objective To investigate the effect of neuropeptide Y (NPY) on the osteoblastic dif-ferentiation of murine MC3T3-E1 cells and its mechanism related to the Wnt signaling pathway. Methods The murine MC3T3-E1 cells were divided into 4 groups according to the stimulators added: phosphate buffered saline (PBS) (control) and different concentrations of NPY (10-8 mol/L, 10-10 mol/L and 10-12 mol/L). The cellular proliferation was detected with MTT assay after 1, 3, 5, 7 and 9 days. The cells were identified with cell immunochemistry and Western Blot to find out the most effective concentration of NPY at different time points under osteoblastic condition. The cells were then divided into 4 groups: PBS, NPY, NPY+NPY receptor antagonist, and NPY+DKK1. Western blot was used to determine the expression of β-catenin and p-GSK-3β in each group. Nuclear signaling activity of β-catenin was observed using immunofluorescence staining. Results NPY significantly improved the proliferation of MC3T3-E1 cells at 7 and 9 days (P< 0.05). NPY (10-8 mol/L and 10-10 mol/L) groups and NPY (10-10 mol/L and 10-12 mol/L) groups signif-icantly improved the ALP activity at 4 and 14 days respectively (P< 0.05). At 4 days, the expression of ALP protein was significantly decreased in the NPY+DKK1 group and the NPY+NPY receptor antagonist group compared with that in the NPY group (P< 0.05). Although the expression levels of β-catenin and p-GSK-3β protein were uninfluenced in either case, NPY significantly stimulated the nuclear signaling activity of β-catenin. Conclusions NPY may significantly increase the expression of ALP protein in MC3T3-E1 cells during osteoblastic differentiation. This effect might be mediated through the canonical Wnt signaling pathway. Key words: Neuropeptide Y; Mice; Cell proliferation; Cell differentiation; Murine MC3T3-E1 cells

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways.

Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH). First, we found that ArcN NPY/AgRP fibers closely appose PVN and DMH presympathetic neurons. Second, nanoinjections of NPY or an NPY receptor Y1 (NPY1R) antagonist into PVN or DMH decreased or increased SSNA, respectively. Third, blockade of DMH NPY1R reversed the sympathoinhibition elicited by selective, DREADD-mediated activation of ArcN NPY/AgRP neurons. Finally, stimulation of ArcN NPY/AgRP terminal fields in the PVN and DMH decreased SSNA. Considering that chronic obesity decreases ArcN NPY content, we propose that the ArcN NPY neuropathway to the PVN and DMH is pivotal in obesity-induced elevations in SNA.

A high fat diet enhances the sensitivity of chick adipose tissue to the effects of centrally injected neuropeptide Y on gene expression of adipogenesis-associated factors

The purpose of this study was to determine how dietary macronutrient composition and exogenous neuropeptide Y (NPY) affect mRNA abundance of factors associated with lipid metabolism in chick adipose tissue. Chicks were fed one of three isocaloric (3000kcal metabolizable energy (ME)/kg) diets after hatch: high carbohydrate (HC; control), high fat (HF; 30% of ME from soybean oil) or high protein (HP; 25% crude protein). On day 4 post-hatch, vehicle or 0.2nmol of NPY was injected intracerebroventricularly and abdominal and subcutaneous fat depots collected 1h later. In abdominal fat, mRNA abundance of peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid binding protein 4 (FABP4) increased after NPY injection in HF diet-fed chicks. NPY injection decreased expression of PPARγ and sterol regulatory element-binding transcription factor 1 (SREBP1) in the subcutaneous fat of HC diet-fed chicks, whereas SREBP1 expression was increased in the subcutaneous fat of HF diet-fed chicks after NPY injection. An acutely increased central concentration of NPY in chicks affects adipose tissue physiology in a depot- and diet-dependent manner. The chick may serve as a model to understand the relationship between diet and the brain-fat axis' role in maintaining whole body energy homeostasis, as well as to understand metabolic distinctions among fat depots.

The role of neuropeptide-Y in nandrolone decanoate-induced attenuation of antidepressant effect of exercise.

Since the increased prevalence of anabolic androgenic steroids abuse in last few decades is usually accompanied by various exercise protocols, the scope of our study was to evaluate the effects of chronic nandrolone decanoate administration in supraphysiological dose and a prolonged swimming protocol (alone and simultaneously with nandrolone decanoate) on depressive state in male rats. Simultaneously, we investigated the possible alterations in neuropeptide Y (NPY) content in blood and the hippocampus, in order to determine the role of NPY in the modulation of depressive-like behavior.Exercise induced antidepressant effects in tail suspension test (decrease of the total duration of immobility), as well as significant increase in the number of hippocampal NPY-interneurons in CA1 region. Chronic nandrolone decanoate treatment attenuated the beneficial antidepressant effects of exercise as measured by the tail suspension test parameters. Simultaneously, nandrolone decanoate treatment resulted in diminution of NPY content both in blood (decreased serum levels) and in hippocampus (the significant decrease in NPY expression in all three investigated hippocampal regions—CA1, CA2/3 and DG). Our findings indicate that alterations in serum and hippocampal NPY contents may underlie the changes in depressive state in rats. The exercise was beneficial as it exerted antidepressant effect, while chronic nandrolone decanoate treatment resulted in depressive-like behavior. Furthermore, the behavioral indicators of depression showed strong correlations with the serum levels and the hippocampal content of NPY.

Role of sympathetic cotransmitter galanin on autonomic balance in heart failure: an active player or a bystander?

Objective:Galanin, a cotransmitter similar to neuropeptide Y (NPY), aggravates autonomic imbalance in systolic heart failure (HF) by attenuating vagal tonus after burst sympathetic activity. In animal HF models, galanin antagonists have improved cardiac function. To determine whether galanin is a promising therapeutic target in HF, we studied its concentrations in HF patients and evaluated its correlation with NPY, markers of humoral activity such as pro-BNP and copeptin, and echocardiographic parameters of HF severity.Methods:After recording demographic and echocardiographic characteristics of 87 individuals (57 HF patients and 30 control subjects), fasting serum concentrations of galanin, NPY, copeptin, and pro-BNP were determined.Results:Unlike pro-BNP, copeptin, and NPY, which were significantly elevated in HF patients (p<0.001, p<0.001, and p=0.001, respectively), galanin was similar in HF patients and control subjects (p=0.9). NPY correlated with the echocardiographic parameters of HF severity (r=–0.22, p=0.03 for EF; r=0.3, p=0.005 for Tei index of RV; r=–0.23, p=0.03 for TAPSE; and r=0.24, p=0.024 for E/e¢) and pro-BNP (r=0.22, p=0.046). NPY levels were also associated with beta blocker (BB) use, wherein BB significantly decreased NPY in both HF patients and control subjects. Galanin correlated with humoral biomarkers, pro-BNP and copeptin (r=0.39, p<0.001 and r=0.41, p<0.001, respectively). Although current smoking, BB therapy, pro-BNP, copeptin, and body mass index were associated with galanin in univariate analyses, the multiple linear regression model revealed that pro-BNP was the only significant determinant of galanin levels in HF patients.Conclusion:Our findings confirmed the role of NPY in autonomic balance and suggest that galanin is associated with the proadrenergic state, but its role in HF in humans remains unclear.

Comparison of the effect of low-frequency electroacupuncture on serum leptin and NPY contents of male and female patients with simple obesity

ObjectiveTo explore the difference of low-frequency electroacupuncture in regulating serum leptin and neuropeptide Y (NPY) of male and female patients with simple obesity due to spleen deficiency and damp exuberance. MethodsEighty patients with simple obesity, including 37 males and 43 females, were included in this study. In both groups (male group and female group), Yīnlíngquán (▪ SP 9), Sānyīnjiāo (▪ SP 6), Zúsānl (▪ ST 36), Fēnglóng (▪ ST 40), Qūchí (▪ LI 11), Tiānshū (▪ ST 25), Zhōngwăn (▪ CV 12), Shuľfěn (▪ CV 9), Qìhăi (▪ CV 6), and Guānyuán (▪ cv 4). were selected, and low-frequency electroacupuncture treatment was applied. Needles were retained for 30 min. The treatment was conducted once a day, and 10 times were considered as one course of treatment. Two courses were needed. The changes of weight, BMI (body mass index), F% (fat percentage) and serum leptin and NPY contents of patients in the two groups before and after treatment were observed and analyzed comparatively. ResultsAfter treatment, in male group, the weight lost (9.24±2.55) kg, BMI reduced by 4.19±2.30, F% reduced by 3.98±2.13, serum leptin level reduced by (0.66±0.23) ng/mL, and serum NPY level reduced by (18.56±2.89) pg/mL; in female group, the weight lost (6.77±2.31) kg, BMI reduced by 2.65±0.93, F% reduced by 4.98±2.30, serum leptin level reduced by (3.49±1.09) ng/mL, and serum NPY level reduced by (11.21±1.97) pg/mL. The results reduced significantly when compared with the level before treatment (P<0.05, P<0.01). The loss of weight, BMI and serum NPY content in male group was more obvious than that in female group (all P<0.01), and the loss of F% and serum leptin content in female group was more obvious than that in male group (both P<0.01). ConclusionLow-frequency electroacupuncture can significantly regulate the weight, BMI, F% and serum leptin and NPY contents of male and female patients with simple obesity, and there are gender differences. In terms of reducing weight, BMI and serum NPY content, the efficacy of low-frequency electroacupuncture in males is superior to that in females, while in terms of reducing F% and serum leptin content, the efficacy in females is superior to that in males.

Association study of arcuate nucleus neuropeptide Y neuron receptor gene variation and serum NPY levels in clozapine treated patients with schizophrenia

BackgroundAntipsychotic-induced weight gain (AIWG) leads to metabolic consequences and comorbidity, social stigmatization and nonadherence in patients with schizophrenia. Neuropeptide Y (NPY) has an important role in appetite and body weight regulation. Associations between AIWG and serum NPY levels, and genetic polymorphisms (SNPs) associated with its serum levels have been little studied in these patients. Subjects and methodsAssociations between serum NPY concentration and other metabolic and inflammatory markers, and 215 SNPs in 21 genes (NPY gene, NPY receptor genes and genes encoding arcuate nucleus NPY neuron receptors) were studied in 180 patients with schizophrenia on clozapine treatment. ResultsThe serum levels of NPY correlated with levels of resistin (r=0.31, P<0.001) and age (r=0.22, P=0.003). In the general linear univariate model the best-fitting model with explanatory factors age, serum resistin level, serum insulin level, BMI and gender explained 18.0% (P<0.001) of the variance of serum NPY. Genetic risk score (GRSNPY) analysis found twelve significant (P<0.05) serum NPY concentration related SNPs among α7 nicotinic acetylcholine receptor gene CHRNA7, insulin receptor gene INSR, leptin receptor gene LEPR, glucocorticoid receptor (GR) gene NR3C1, and NPY gene. However, after permutation test of gene score the predictive value of GRSNPY remained non-significant (P=0.078). ConclusionsSerum NPY level does not seem to be a feasible biomarker of AIWG. Serum NPY level alterations are not significantly associated with the candidate gene polymorphisms studied.