Neuropeptide Y Levels Research Articles

Effects of Moxonidine Administration on Serum Neuropeptide Y Levels in Hypertensive Individuals: A Prospective Observational Study

Moxonidine is a centrally acting, anti-hypertensive medication that exerts additional metabolic properties. It is unknown whether its effects are mediated by neurotransmitters or sympathetic tone regulators, including Neuropeptide Y (NPY). In this study, we evaluated the effects of moxonidine administration on serum NPY in humans. Methods: Ninety individuals with mild or moderate arterial hypertension that required monotherapy were categorized in three age and gender-matched groups according to their Body Mass Index (BMI) as normal weight (n = 30), overweight (n = 30), and obese (n = 30). Moxonidine was administered in therapeutic doses of up to 0.6 mg daily for 12 weeks, and clinical, biochemical and hormonal parameters were recorded. Results: In all three groups, a decrease in systolic and diastolic blood pressure and heart rate was shown. After treatment, BMI, 24 h urine catecholamines and catecholamines’ metabolites, and serum total cholesterol were also reduced. Most importantly, we found a decrease in serum NPY levels in all study groups, with the largest mean decrease in the group of obese and overweight participants compared to normal weight. Conclusions: Moxonidine administration results in improvement in cardio-metabolic parameters, as well as a decrease in serum NPY levels, which therefore represents it being a potent agent against obesity-associated hypertension. Its involvement in energy balance regulation warrants further investigation.

Diagnostic role of NPY methylation in patients with colorectal cancer

<sec><i>Objectives</i>: A growing number of studies have shown that methylation biomarkers play an important role in oncogenesis. This study aimed to explore the diagnostic role of neuropeptide Y (NPY) methylation in colorectal cancer (CRC).</sec><sec><i>Methods</i>: mRNA and protein expression, methylation, survival benefits, and immune cell infiltration were analyzed using bioinformatics tools across all tumors from The Cancer Genome Atlas. NPY methylation in CRC was further validated in CRC tissues, fecal samples, and cell lines. Analyses of NPY methylation were performed using Sequenome EpiTYPER and quantitative PCR. Retrieval of NPY expression in cell lines was tested using real-time PCR and western blotting.</sec><sec><i>Results</i>: Bioinformatic analysis showed that the methylation level of NPY increased in most carcinomas (<i>P</i><0.05). Moreover, statistical correlations were observed between NPY transcriptional expression and CD4<sup>+</sup> T cells, macrophages, and dendritic cells in colon cancer (<i>P</i><0.05). Similar results were obtained for CD4<sup>+</sup> T cells, neutrophils, and NPY in rectal cancer (<i>P</i><0.05). Our results showed that NPY was hypermethylated in CRC tissues and fecal exfoliated cells (<i>P</i><0.05). Fecal NPY methylation was observed in 82.5% sensitive for primary tumors, 46.3% for intestinal polyps (including adenomatous, serrated, and inflammatory polyps), and 23.4% of healthy controls. Overall, fecal NPY methylation was 76.6% specific. For cell lines, in vivo experiments demonstrated that 5-aza-2′-deoxycytidine downregulated the methylation of NPY and restored its mRNA level (<i>P</i><0.05).</sec><sec><i>Conclusions</i>: This study indicates that NPY is hypermethylated in CRC, and that NPY methylation in fecal DNA is a potential noninvasive diagnostic biomarker for Chinese patients with CRC.</sec>

Neuropeptide Y as a potential biomarker in patients with asthma and obesity

The phenotype of asthma with obesity is particularly difficult to treat, while its prevalence is increasing. In recent years, special attention has been paid to neuropeptide Y (NPY) due to its possible effect on the severity of the clinical course of asthma. Aim. To identify the relationship between the level of NPY and the clinical course of asthma in patients with obesity and overweight. Methods. The study included 113 patients (27, or 23.89% of men and 86, or 76.11% of women) diagnosed with asthma of moderate severity, whose average age was 57.81 ± 13.05 years. Patients were divided into three groups — with normal body weight, overweight, and obesity. The examination included spirometry, body mass index (BMI), and a questionnaire. Also, Asthma Control Test (ACT) was used. The levels of leptin, adiponectin, NPY, and general oxidative damage were measured in all patients. Results. Asthma control was significantly lower in the group of patients with asthma and obesity compared with the normal body weight and overweight patients. Leptin level was significantly higher in the group of patients with asthma and obesity compared with the normal body weight and overweight patients. The level of NPY was significantly higher in the group of patients with obesity than in the patients with normal body weight and overweight. No significant differences in the level of adiponectin were found between the groups. The NPY level had a high inverse correlation with VLC index, a moderate/medium inverse correlation with forced expiratory volume in 1 sec, forced expiratory flow (FEF) at 25%; forced vital capacity, Tiffno index, FEF 50%, peak expiratory flow, ACT score, and a moderate positive correlation with the level of total oxidative damage. Conclusion. A higher level of NPY is observed in patients with asthma and obesity. This level has an inverse correlation with spirometric parameters, asthma control (evaluated via ACT) and a positive correlation with the level of general oxidative damage, which indicates a possible proinflammatory effect of NPY that contributes to an unfavorable course of asthma. Thus, further studies are required to establish the nature of the relationship between NPY and asthma exacerbations, as well as the mechanism of NPY influence on asthma pathogenesis.

Characteristic expression of CGRP and osteogenic and vasculogenic markers in the proximal and distal regions of the rib during male mouse development

BackgroundNeuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis and osteogenesis during bone formation and organ development. From the foetal period to the postnatal period, the thorax, which is necessary for lung respiration, forms. The thorax exhibits the same cartilage ossification as the bones of the extremities, but a specific system within the thorax exists as costal cartilage after birth. The relationship among CGRP, osteogenesis and vasculogenic markers in the two rib locations during thorax formation is not fully understood. Materials and methodsIn our study, male mice were used to provide ribs under different development conditions on various embryonic days (E12. 5, E14.5, and E17.5) and postnatal days (P1 and P5). The mRNA expression levels of CGRP, vascular endothelial growth factor (VEGF-A), type 1 collagen (Col1a-1), type 2 collagen (Col2a1), neuropeptide Y (NPY), osteocalcin (OCN) and osteopontin (OPN) were analysed by qRT-PCR. We also analysed the mRNA expression of CGRP, VEGF-A and OPN by in situ hybridization. Multivariate modelling with principal component analysis (PCA) was performed to estimate the interactions among the quantitative real-time RT-PCR data. ResultsThe mRNA expression levels of CGRP, VEGF-A, Col2a, Col1a-1, OCN, and NPY in the male mouse rib gradually increased during development. An antisense probe for CGRP mRNA was strongly detected in the central region of the mouse rib at E12.5 and the hypertrophic and ossification zones at E17.5 by in situ hybridization. VEGF-A was also located in the same region as CGRP at E12.5 and E17.5. OPN was strongly detected at the rib formation stage from E14.5 to E17.5. The expression of CGRP also differed between the proximal and distal regions of the rib at E17.5. As demonstrated by in situ hybridization, CGRP continuously participates in cartilage formation in the distal regions of the rib after birth. The PCA revealed that the mRNA expression of CGRP was related to that of Col1a-1 and VEGF-A during rib formation. ConclusionThis study shows that CGRP is involved in vascular and bone formation during rib development and may also be involved in cartilage formation after birth. The findings suggest that CGRP may temporarily participate in bone formation and continuously participate in cartilage formation in the rib, which may also be related to the formation of the anterior thoracic wall after birth

Neuropeptide Y Variation Is Associated With Altered Static and Dynamic Functional Connectivity of the Salience Network.

Neuropeptide Y (NPY) is a neurotransmitter that has been implicated in the development of anxiety and mood disorders. Low levels of NPY have been associated with risk for these disorders, and high levels with resilience. Anxiety and depression are associated with altered intrinsic functional connectivity of brain networks, but the effect of NPY on functional connectivity is not known. Here, we test the hypothesis that individual differences in NPY expression affect resting functional connectivity of the default mode and salience networks. We evaluated static connectivity using graph theoretical techniques and dynamic connectivity with Leading Eigenvector Dynamics Analysis (LEiDA). To increase our power of detecting NPY effects, we genotyped 221 individuals and identified 29 healthy subjects at the extremes of genetically predicted NPY expression (12 high, 17 low). Static connectivity analysis revealed that lower levels of NPY were associated with shorter path lengths, higher global efficiency, higher clustering, higher small-worldness, and average higher node strength within the salience network, whereas subjects with high NPY expression displayed higher modularity and node eccentricity within the salience network. Dynamic connectivity analysis showed that the salience network of low-NPY subjects spent more time in a highly coordinated state relative to high-NPY subjects, and the salience network of high-NPY subjects switched between states more frequently. No group differences were found for static or dynamic connectivity of the default mode network. These findings suggest that genetically driven individual differences in NPY expression influence risk of mood and anxiety disorders by altering the intrinsic functional connectivity of the salience network.

Metabolic Consequences of Neuronal HIF1α-Deficiency in Mediobasal Hypothalamus in Mice.

ObjectiveThis study aims to investigate whether hypoxia-inducible factor 1α (HIF1α) in the neurons of the mediobasal hypothalamus is involved in the regulation of body weight, glucose, and lipid metabolism in mice and to explore the underlying molecular mechanisms.MethodsHIF1α flox/flox mice were used. The adeno-associated virus that contained either cre, GFP and syn, or GFP and syn (controls) was injected into the mediobasal hypothalamus to selectively knock out HIF1α in the neurons of the mediobasal hypothalamus. The body weight and food intake were weighed daily. The levels of blood glucose, insulin, total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)were tested. Intraperitoneal glucose tolerance test (IPGTT) was performed. The insulin-stimulated Akt phosphorylation in the liver, epididymal fat, and skeletal muscle were examined. Also, the mRNA expression levels of HIF1α, proopiomelanocortin (POMC), neuropeptide Y (NPY), and glucose transporter protein 4 (Glut4) in the hypothalamus were checked.ResultsAfter selectively knocking out HIF1α in the neurons of the mediobasal hypothalamus (HIF1αKOMBH), the body weights and food intake of mice increased significantly compared with the control mice (p < 0.001 at 4 weeks). Compared with that of the control group, the insulin level of HIF1αKOMBH mice was 3.5 times higher (p < 0.01). The results of the IPGTT showed that the blood glucose level of the HIF1αKOMBH group at 20–120 min was significantly higher than that of the control group (p < 0.05). The serum TC, FFA, HDL, and LDL content of the HIF1αKOMBH group was significantly higher than those of the control group (p < 0.05). Western blot results showed that compared with those in the control group, insulin-induced AKT phosphorylation levels in liver, epididymal fat, and skeletal muscle in the HIF1αKOMBH group were not as significantly elevated as in the control group. Reverse transcription-polymerase chain reaction (RT-PCR) results in the whole hypothalamus showed a significant decrease in Glut4 mRNA expression. And the mRNA expression levels of HIF1α, POMC, and NPY of the HIF1αKOMBH group decreased significantly in ventral hypothalamus.ConclusionsThe hypothalamic neuronal HIF1α plays an important role in the regulation of body weight balance in mice under normoxic condition. In the absence of hypothalamic neuronal HIF1α, the mice gained weight with increased appetite, accompanied with abnormal glucose and lipid metabolism. POMC and Glut4 may be responsible for this effect of HIF1α.

Effects of ultrasound-guided erector spinae plane block on the immune function and postoperative recovery of patients undergoing radical mastectomy.

To explore the effects of ultrasound-guided erector spinae plane (ESP) block on the immune function and postoperative recovery of patients undergoing radical mastectomy. One hundred and four patients with breast cancer were randomly divided into the observation group and control group, with 52 cases in each group. The control group underwent induction of routine general anesthesia and thoracic paravertebral block, while the observation group underwent ultrasound-guided ESP block combined with general anesthesia. The recovery of autonomous respiration, eye opening, extubation time, postoperative eating, first anal exhaust, leaving bed and hospitalization time in both groups were statistically analyzed after surgery. The immune function indexes [CD4+, CD8+, interferon-γ (IFN-γ)] and the expression levels of serum neuropeptide Y (NPY), prostaglandin E2 (PGE2) and serotonin (5-HT) were compared between the two groups at 24 and 48 h before and after surgery. The visual analog scale (VAS) scores at rest and during exercise were recorded at 6, 12, 24, and 48 h after surgery. There was no significant difference in the recovery of autonomous respiration, eye opening, and extubation time between the two groups (P>0.05). However, postoperative eating, first anal exhaust, leaving bed, and hospitalization time in the observation group were shorter than those in the control group (P<0.05). At 24 and 48 h after surgery, compared with the control group, CD4+ and IFN-γ levels were increased significantly (P<0.05), CD8+ and levels of serum NPY, PGE2, 5-HT and the incidence of postoperative complications was decreased significantly in the observation group (P<0.05). VAS scores at rest and during exercise in the observation group were lower than those in the control group (P<0.05). At 5 and 10 min after intubation, the observation group had higher epinephrine (E) level and lower serum cortisol (Cor) level than the control group (P<0.05). The analgesic effect of ultrasound-guided ESP block is significant after radical mastectomy. There are few adverse reactions and few effects on immune function, and it can promote the postoperative recovery of patients.

Intranasal Neuropeptide Y as a Potential Therapeutic for Depressive Behavior in the Rodent Single Prolonged Stress Model in Females.

The susceptibility to stress-elicited disorders is markedly influenced by sex. Women are twice as likely as men to develop posttraumatic stress disorder (PTSD), depression, anxiety disorders, and social impairments following exposure to traumatic stress. However, most of the studies in animal models examining putative therapeutics for stress-triggered impairments, including single prolonged stress (SPS), were performed predominantly with males. Previous studies in males demonstrated that intranasal neuropeptide Y (NPY) can provide therapeutic relief of many SPS-triggered behaviors, but is ineffective in females at the same dose. Thus, females may need a higher dose of exogenous NPY to attain a therapeutically significant concentration since the overwhelming majority of studies found that NPY levels in females in many brain regions are lower than in male rodents. Here, we examined SPS as an appropriate model to elicit many PTSD-associated symptoms in females and whether intranasal NPY at higher doses than with males is able to alter the development of SPS-triggered behavioral impairments. Sprague-Dawley female rats were exposed to SPS only, or in a separate cohort after SPS stressors were immediately infused intranasally with one of several doses of NPY, starting with 600 μg/rat—four times the dose effective in males. In the third cohort of animals, females were infused intranasally with either 600 μg NPY, omarigliptin [a dipeptidyl peptidase IV (DPP4) inhibitor], or both right after the SPS stressors. After 19 days they were tested on several behavioral tests. SPS elicited significant depressive/despair like behavior on the forced swim test (FST), anxiety behavior on the elevated plus maze (EPM), as well as impaired social interaction. On the FST, there was a dose-response effect of intranasal NPY, with 1,200 μg, but not 600 μg, preventing the development of the SPS-elicited depressive-like behavior. The omarigliptin and 600 μg NPY combined treatment, but neither alone, was also sufficient at preventing depressive-like behavior on the FST. The results demonstrate that: (1) SPS elicits several behavioral manifestations of PTSD in females; (2) early intervention with a high dose of intranasal NPY has therapeutic potential also for females; and (3) NPY cleavage by DPP4 may play a role in the higher dose requirement for females.

Chronic oral nicotine administration and withdrawal regulate the expression of neuropeptide Y and its receptors in the mesocorticolimbic system

Neuropeptide Y (NPY) and its receptors are involved in the regulation of mood, stress, and anxiety. In parallel, NPY signaling may play a vital role in the negative affective state induced by drug withdrawal. This study examined the changes in the transcript levels of NPY, Y1, Y2, and Y5 receptors in the mesocorticolimbic system during chronic nicotine exposure and withdrawal. Rats were administered with nicotine (initial dose: 25 μg/ml, maintenance dose: 50 μg/ml, free base) in drinking water for 12 weeks. Control group received only tap water. In the final week of the study, some of the nicotine-treated animals continued to receive nicotine (0-W), whereas some were withdrawn for either 24 (24-W) or 48 (48-W) h. All animals were decapitated after the evaluation of somatic signs (frequency of gasps, eye blinks, ptosis, shakes, teeth chatter) and the duration of locomotor activity and immobility. mRNA levels of NPY, Y1, Y2, and Y5 receptors in the mesocorticolimbic system were measured by quantitative real-time PCR (qRT-PCR). Results showed that nicotine withdrawal increased overall somatic signs. Moreover, chronic nicotine treatment increased the duration of locomotor activity, whereas withdrawal increased the duration of immobility. qRT-PCR analysis revealed that chronic nicotine treatment increased NPY mRNA levels in the hippocampus. On the other hand, 24- and 48-h withdrawals increased NPY mRNA levels in the amygdala and medial prefrontal cortex (mPFC), Y1 and Y2 mRNA levels in the nucleus accumbens and mPFC, and Y5 mRNA levels in the mPFC. These findings suggest that nicotine withdrawal enhances NPY signaling in the mesocorticolimbic system, which could be an important mechanism involved in regulating the negative affective state triggered during nicotine withdrawal.

Serum Neuropeptide Y: A Potential Prognostic Marker of Intracerebral Hemorrhage.

Objective Neuropeptide Y (NPY), a 36-amino acid neuromodulator, is mainly secreted by neurons in the central and peripheral nervous systems, which participate in the regulation of a series of physiological processes. However, there are few studies on its correlation with intracranial hemorrhage (ICH). The purpose of this study is to determine whether the serum NPY level is related to the prognosis of ICH. Methods 364 patients diagnosed with ICH were included in the current study. The demographics, anthropometrics, medical history, clinical severity, and laboratory data are collected. Enzyme-linked immunoassay (ELISA) was used to detect the serum NPY level of each patient upon admission. Three months after the occurrence of ICH, we used the modified Rankin scale (mRS) to evaluate the prognosis of patients, and mRS > 2 was defined as a poor prognosis. Results A total of 364 patients with ICH were included in the study, including 140 patients with a good prognosis and 224 patients with a poor prognosis. Compared with patients with a poor prognosis, ICH patients with a good prognosis have a lower baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.036) and smaller hematoma volume (p = 0.039). The results of ELISA showed that compared with patients with a poor prognosis, ICH patients with a good prognosis had lower serum NPY levels (19.4 ± 3.7 vs. 27.6 ± 3.3 ng/ml, p < 0.001). Linear correlation analysis showed that the serum NPY level of ICH patients was significantly positively correlated with the baseline NIHSS score (r = 0.413, p = 0.041) and hematoma volume (r = 0.308, p = 0.026). Receiver operating characteristic (ROC) curve analysis showed that the sensitivity of the serum NPY level to predict the prognosis of ICH was 70.9%, the specificity was 72.6%, and the cut-off value was 24.2 ng/ml. Conclusions The serum NPY level may be used as a predictor of ICH prognosis.

Therapeutic effects of Gambi-jung for the treatment of obesity

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.

A novel mouse model to evaluate neuropeptide Y-mediated melanocyte pathology.

Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to loss of the pigment-producing melanocytes. No cure exists for vitiligo. The available treatments are inefficient for many patients, suggesting that universal treatment approaches may be inappropriate. Deeper understanding of the mechanistic basis for variability in vitiligo aetiologies is necessary. Genetic mutations in neuropeptide Y (NPY), a widely distributed protein, are associated with increased NPY expression and increased susceptibility for vitiligo. NPY is also upregulated in the circulation and lesional skin of some vitiligo patients. However, the contributions of NPY to melanocyte pathology are not understood, and presently there are no models with which to investigate this possibility. In this study, we employed NPY-overexpressing mice to explore the role of NPY in melanocyte dysfunction. Our results show that NPY overexpression induces progressive hair greying (depigmentation) due to premature depletion of follicular melanocyte stem cells. Additionally, NPY transcripts and protein are elevated in the skin and melanocytes of these mice, respectively, suggesting that these effects may be mediated locally. Together, these results suggest that supraphysiological levels of NPY in the skin can induce melanocyte dysfunction, thus identifying this mouse line as a novel model to study NPY-mediated melanocyte pathology.

Comparison of the Agouti Dependent Protein and Neuropeptide Y Response to the High Intensity Interval Training in Obese and Underweight Men

Objective: Appetite regulation has a great impact on energy homeostasis. This study aimed to compare the response agoutirelated protein (AGRP) and neuropeptide Y (NPY) to a single high intensity interval training (HIIT) in obese and underweight men. Materials and Methods: This semi-experimental research conducted on 40 obese and underweight men who were divided into four groups including experimental groups (10 obese, and 10 underweight men) and control groups (10 obese, and 10 underweight controls). Both groups were evaluated by biochemical measurements in two stages of pre-test and post-test. HIIT was carried out to the experimental groups during one session. Data were analyzed using one-way ANOVA and T-test using SPSS 21 software. Results: NPY levels showed a significant difference in pre and post-test in both experimental groups, NPY increased 6.14% in obese men and 25.50% in underweight men, which was significant in both obese (P-value= 0.002) and underweight (P-value= 0.007) groups. In addition, AGRP levels increased 1.91% in obese men and 6.65% in underweight men, although this was not significant (P-value= 0.098). However, no significant differences were observed among groups in the levels of NPY and AGRP (P-value= 0.114). Conclusion: The results of the present study showed that HIIT can increase the amount of AGRP and NPY in obese and underweight men. Therefore, appetite neuropeptides increase after a training session, which should be considered in the balance of energy and food intake after exercise.

CB1 receptor neutral antagonist treatment epigenetically increases neuropeptide Y expression and decreases alcohol drinking

Alcohol consumption is mediated by several important neuromodulatory systems, including the endocannabinoid and neuropeptide Y (NPY) systems in the limbic brain circuitry. However, molecular mechanisms through which cannabinoid-1 (CB1) receptors regulate alcohol consumption are still unclear. Here, we investigated the role of the CB1 receptor-mediated downstream regulation of NPY via epigenetic mechanisms in the amygdala. Alcohol drinking behavior was measured in adult male C57BL/6J mice treated with a CB1 receptor neutral antagonist AM4113 using a two-bottle choice paradigm while anxiety-like behavior was assessed in the light-dark box (LDB) test. The CB1 receptor-mediated changes in the protein levels of phosphorylated cAMP-responsive element binding protein (pCREB), CREB binding protein (CBP), H3K9ac, H3K14ac and NPY, and the mRNA levels of Creb1, Cbp, and Npy were measured in amygdaloid brain structures. Npy-specific changes in the levels of acetylated histone (H3K9/14ac) and CBP in the amygdala were also measured. We found that the pharmacological blockade of CB1 receptors with AM4113 reduced alcohol consumption and, in an ethanol-naïve cohort, reduced anxiety-like behavior in the LDB test. Treatment with AM4113 also increased the mRNA levels of Creb1 and Cbp in the amygdala as well as the protein levels of pCREB, CBP, H3K9ac and H3K14ac in the central and medial nucleus of amygdala, but not in the basolateral amygdala. Additionally, AM4113 treatment increased occupancy of CBP and H3K9/14ac at the Npy gene promoter, leading to an increase in both mRNA and protein levels of NPY in the amygdala. These novel findings suggest that CB1 receptor-mediated CREB signaling plays an important role in the modulation of NPY function through an epigenetic mechanism and further support the potential use of CB1 receptor neutral antagonists for the treatment of alcohol use disorder.

Neuropeptide Y prevents nucleus pulposus cells from cell apoptosis and IL‑1β‑induced extracellular matrix degradation

ABSTRACT Intervertebral disc degeneration (IDD) is characterized by excessive inflammatory reaction, and neuropeptide Y (NPY) was reported to have anti-inflammatory effect. However, the effect of NPY on NP cells has not been investigated up to date. This study aimed to clarify the role of NPY on the process of IDD. Fourteen fresh human lumbar intervertebral discs were harvested, and degeneration-related proteins were examined. Pfirrmann grading system was used to evaluate IDD. Rat nucleus pulposus (NP) cells were used to investigate the effect of NPY on the proliferation, apoptosis, and extracellular matrix (ECM) in NP cell induced by IL-1βin vitro. The expression levels of NPY and its receptors (type 1 receptor, Y1R, and type 2 receptor, Y2R) were detected via immunohistochemical analysis, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and proliferation were explored using cell counting kit-8 assay, western blot, and immunofluorescence analysis. Cell apoptosis was investigated by Hoechst staining, JC-1 Staining, annexin V-FITC/PI double staining, and western blot. The secretion of NPY from NP cells was determined via enzyme-linked immunosorbent assay (ELISA). The expression of anabolic and catabolic gene was analyzed by qRT-PCR, western blot, immunofluorescence analysis, and ELISA. The expression of Y2R was significantly increased in both human degenerative intervertebral discs and IL-1β-induced NP cells. Although no positive results for NPY indicated by western blot both in vivo and in vitro, ELISA results demonstrated that the secretion of NPY from NP cells was increased by low-concentration IL-1β, but was decreased when the concentration of IL-1β was 30 ng/ml and above. In addition, NPY could promote NP cells proliferation and protect NP cells against IL‑1β‑induced apoptosis via suppressing mitochondrial-mediated apoptosis pathway. What’s more, NPY can suppress the expression of catabolic gene and ameliorate IL-1β- induced matrix degeneration in NP cells. In conclusion, NPY could promote NP cell proliferation and alleviate IL‑1β‑induced cell apoptosis via mitochondrial pathway. In addition, NPY can suppress the expression of ECM‑catabolic proteinases and ameliorate IL-1β- induced ECM degeneration in vitro.

Relationship between Tumor Necrosis Factor-Alpha and Neuropeptide Y Expression and Neurological Function Score in Epileptic Children.

Background:To observe the relationship between Tumor Necrosis Factor-alpha (TNF-α) and Neuropeptide Y (NPY) expression and neurological function score in epileptic children.Methods:Fifty-four epileptic children diagnosed and treated in Xuzhou Children’s Hospital, China from Feb 2017 to Mar 2018 were collected and included in a research group (RG), while 30 healthy children who underwent physical examination at the same time were included in the control group (CG). ELISA was used to detect the expression of TNF-α and NPY in the serum of children in the two groups, and those before treatment were compared. The National Institute of Health stroke scale (NIHSS) and Hamilton Anxiety (HAMA) scores before and after treatment were observed, and Pearson correlation was used to analyze the relationship between the expression levels of TNF-α and NPY in the serum as well as NIHSS and HAMA scores.Results:The expression levels of TNF-α and NPY in the serum of children in the RG were significantly higher than those in the CG (P<0.001). The expression level of TNF-α was positively correlated with the NIHSS and HAMA scores (r=0.748, P<0.001) (r=0.772, P<0.001). The expression level of NPY was positively correlated with the NIHSS and HAMA scores (r=0.768, P<0.001) (r=0.643, P<0.001).Conclusion:TNF-α and NPY are highly expressed in epileptic children and are positively correlated with neurological function score.

Regulation of Pancreatic β-Cell Function by the NPY System.

The neuropeptide Y (NPY) system has been recognized as one of the most critical molecules in the regulation of energy homeostasis and glucose metabolism. Abnormal levels of NPY have been shown to contribute to the development of metabolic disorders including obesity, cardiovascular diseases, and diabetes. NPY centrally promotes feeding and reduces energy expenditure, while the other family members, peptide YY (PYY) and pancreatic polypeptide (PP), mediate satiety. New evidence has uncovered additional functions for these peptides that go beyond energy expenditure and appetite regulation, indicating a more extensive function in controlling other physiological functions. In this review, we will discuss the role of the NPY system in the regulation of pancreatic β-cell function and its therapeutic implications for diabetes.

Effects of light cycle on circadian feeding activity and digestive physiology in Haliotis discus hannai

The abalone Haliotis discus hannai is a typical nocturnal animal. It generally feeds and moves at night but evades light by hiding in the shade during the day. However, the effects of different light cycles on the feeding physiology and potential molecular mechanisms responsible for such effects in H. discus hannai have not yet been reported. We examined the feeding patterns of abalones under different light (L)/dark (D) cycles (0 L:24D, 12 L:12D, 24 L:0D) using an infrared camera and analyzed the relationships between circadian digestive enzyme activities, gene expression levels of neuropeptide Y (NPY) and its receptor (NPYR), which can promote appetite, and feeding rhythms. Feeding in abalones, including searching for food and, food capture and intake, was examined by observation of videos. The percentage of abalones feeding under different light/dark cycles had two peaks, at 20:00–22:00 and 02:00–04:00. The ingestion rate was significantly higher in abalones maintained under 12 L:12D compared with 24 L:0D conditions. The percentage of feeding individuals and food intake were significantly lower in the “daytime” compared with at “night” irrespective of the light/dark cycle, suggesting the existence of an independent internal timing mechanism and the possible involvement of circadian clock genes in the regulation of periodic feeding activity in abalones. In abalones maintained under 12 L:12D and 24 L:0D cycles, protease, cellulase, and α-amylase activities started to increase from 18:00, 2 h before the first peak of food intake. Expression levels of NPY peaked at 20:00 and expression levels of NPYR increased again at 04:00, suggesting that NPY and NPYR might be induced before and after the two peak periods of food intake in abalones, respectively. These findings demonstrate the feeding rhythm and ingestion rate of abalones under different light/dark cycles, as well as the relationships among digestive enzyme activities, gene expression levels of NPY and NPYR, and feeding activity, which in turn provides a useful reference for the development of optimal feeding strategies and improved food utilization in abalone aquaculture production.

Effect of intranasal acupuncture on neurogenic inflammation in allergic rhinitis rabbits

To observe the effect of intranasal acupuncture on allergic rhinitis (AR), and expression of substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) proteins in the nasal mucosa and contents of serum immunoglobulin E (IgE), interleukin 4 (IL-4) and interferon-γ (IFN-γ) in AR rabbits, so as to explore its mechanisms underlying improvement of AR. New Zealand rabbits were randomly divided into normal control, AR model, non-acupuoint acupuncture (NAA) and intranasal acupuncture (INA) groups, with 8 rabbits in each group. The AR model was established by intra-peritoneal injection of egg protein and nasal mucosal stimulation. In the INA group, bilateral "Neiyingxiang" (EX-HN9) within the nasal cavity (the anterior attachment area of the inferior turbinate, about 1 cm away from the nasal limen) were acupunctured by mani-pulating the filiform needles for a while with uniform reinforcing and reducing methods, followed by keeping the needles for 20 min. In the NAA group, shallow acupuncture was applied to the skin of the outer margin of the cheeks, followed by keeping the needle for 20 min. The acupuncture treatment was conducted once every other day for 7 days. The symptoms of sneezing frequency, nasal secretion amount and nasal itching were scored. The expression levels of SP, VIP and NPY in the nasal mucosa tissue were detected by immunohistochemistry, and the serum IgE, IL-4, and IFN-γ contents were detected by ELISA. After modelling, the symptom score, expression of SP and VIP, and serum IgE and IL-4 contents were significantly higher (P<0.01,P<0.05), NPY expression and serum IFN-γ content significantly lower (P<0.05, P<0.01) in the model group than in the normal control group. Following the intervention, the symptom scores, expressions of SP and VIP, and serum IgE and IL-4 contents were remarkably decreased (P<0.05, P<0.01), while the NPY expression and serum IFN-γ content were significantly up-regulated (P<0.05, P<0.01) in the INA group than in the model group. The effects of INA group were significantly superior to those of NAA group in reducing symptom score, SP and VIP expression, and serum IgE and IL-4 contents and up-regulating NPY expression and IFN-γcontent (P<0.05, P<0.01). There were a positive correlation between the expressions of SP and VIP and contents of serum IgE and IL-4 (P<0.05), and a negative correlation between the expressions of SP and VIP and IFN-γ content (P<0.05). INA treatment can relieve symptoms of AR in AR rabbits, which may be associated with its effects in regulating the expression of SP, VIP and NPY of the nasal mucosa, and contents of serum IgE, IL-4 and IFN-γ to improve neurogenic inflammation.

Neuropeptide Y and Peptide YY in Association with Depressive Symptoms and Eating Behaviours in Adolescents across the Weight Spectrum: From Anorexia Nervosa to Obesity.

Neuropeptide Y (NPY) and peptide YY (PYY) are involved in metabolic regulation. The purpose of the study was to assess the serum levels of NPY and PYY in adolescents with anorexia nervosa (AN) or obesity (OB), as well as in a healthy control group (CG). The effects of potential confounders on their concentrations were also analysed. Eighty-nine adolescents were included in this study (AN = 30, OB = 30, and CG = 29). Anthropometric measurements and psychometric assessment of depressive symptoms, eating behaviours, body attitudes, and fasting serum levels of NPY and PYY were analysed. The AN group presented severe depressive symptoms, while the OB group held different attitudes towards the body. The levels of NPY were lower in the AN and OB groups as compared with the CG. The PYY levels were higher in the OB group than in the AN group and the CG. The severity of eating disorder symptoms predicted fasting serum concentrations of NPY. Lower levels of NPY in AN, as well as in OB suggests the need to look for a common link in the mechanism of this effect. Higher level of PYY in OB may be important in explaining complex etiopathogenesis of the disease. The psychopathological symptoms may have an influence on the neurohormones regulating metabolism.