Injection Of NPY Research Articles

Dietary macronutrient composition and central neuropeptide Y injection affect dietary preference and hypothalamic gene expression in chicks

Objective: The objective of this study was to determine the influence of dietary macronutrient composition on central NPY's orexigenic effect in chicks.Methods: Day-of-hatch chicks were fed one of three diets (3000 kcal ME/kg) ad libitum from hatch: high carbohydrate (HC), high fat (HF; 30% ME derived from soybean oil), and high protein (HP; 25 vs. 22% CP). In Experiment 1, chicks received intracerebroventricular injections of 0 (vehicle), 0.2, or 2.0 nmol NPY on day 4 and food intake was recorded for 6 hours. In Experiment 2, chicks were given all three diets before and after injection. In Experiment 3, hypothalamus was collected at 1-hour post-injection for gene expression analysis.Results: The HC diet-fed chicks responded with a greater increase, while the chicks fed the HF diet had a lower threshold response in food intake to NPY. Neuropeptide Y dose-dependently increased food intake in chicks fed the HC and HP diets. Chicks administered 0.2 nmol NPY preferred the HC and HP diets over the HF diet. Relative quantities of hypothalamic NPYR1 and MC4R mRNA were reduced by NPY in chicks that consumed the HP and HC diets, respectively.Discussion: Consumption of the HC diet was associated with the most robust NPY-induced increase in food intake. Injection of NPY accentuated differences among dietary groups in hypothalamic gene expression of several appetite-associated factors, results suggesting that the NPY/agouti-related peptide and melanocortin pathways are associated with some of the diet- and NPY-induced differences observed in this study.

Why one enters torpor: focus on “NPY Y1 receptor antagonist prevents NPY-induced torpor-like hypothermia in cold-acclimated Siberian hamsters”

neuropeptide y (npy) has long been known to play a major role in mediating energy balance. Intracerebral ventricular injection of NPY results in a vigorous feeding response and is perhaps the most orexigenic compound studied to date ([3][1]). NPY expression is robustly elevated within the

Time-Course Changes of Hormones and Cytokines by Lipopolysaccharide and Its Relation with Anorexia

We assessed the time course effects of lipopolysaccaride (LPS) on food intake, cytokines, and hormones in rats and evaluated the relation between LPS-induced anorexia and its possible causative factors. Food intake was reduced 2 h after LPS injection (500 microg/kg, intraperitoneally) and remained decreased for 24 h. Plasma TNF-alpha and IL-6 levels increased by LPS administration at 0.5 and 2 h, and at 2 and 4 h, respectively. Plasma leptin and glucose levels were elevated at 8 and 16 h, and insulin levels were elevated at 2, 4, 8, and 16 h in the LPS-injected group, as compared to the counterpart controls. IL-6 levels in the CSF were elevated at 2 and 4 h. Hypothalamic cytokines tended to increase as early as 0.5 h after LPS injection and remained increased until 16 h. LPS-induced anorexia was attenuated in insulin-deficient STZ rats and was abolished by insulin treatment. The hypothalamic expression of NPY, a target of insulin's anorexic effect, was decreased 2 h after LPS administration, and central NPY injection (3 nM) prevented LPS-induced anorexia. In conclusion, cytokines, insulin, and leptin levels evidence different time courses by LPS administration. In LPS-induced anorexia, insulin may constitute a newly found causative factor, whereas leptin appears to be uninvolved in an early period in rats.

Anti-nociceptive role of neuropeptide Y in the nucleus accumbens in rats with inflammation, an effect modulated by mu- and kappa-opioid receptors*

Abstract Recent study in our laboratory showed that neuropeptide Y (YPY) plays an antinociceptive role nucleus accumbens (NAc) in intact rats. The present study was performed to further investigate the effect of NPY in nociceptive modulation in the NAc of rats with inflammation, and the possible interation between NPY and the opioid systems. Experimental inflammation was induced by subcutanceous injection of carrageenan into the left hindpaw of rats. Intra-NAc administration fo NPY induced a dose-dependent increase of hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in rats with inflammation. The anti-nociceptive effect of Y1 receptor in the NPY-induced anti-nociception. Furthermore, intra-NAc injection of N1 receptor antagonist NPY28-36, suggesting an involvement of antagonized the increased HWLs induced by preceding intra-NAc administration of the opioid antagonist nalozone signigicantly antagonized the increased HWLs induced by preceding intra-NAc injection of NPY, suggesting ...

Neuropeptide Y administered into cerebral ventricles stimulates sucrose ingestion in the near-term ovine fetus

Objective In adults, nutrient intake is controlled by opposing actions of appetite stimulants (eg, neuropeptide Y [NPY]) and suppressors (eg, leptin). Because NPY may exert a preferential role in mediating adult carbohydrate intake, we sought to determine the effect of central NPY on near-term fetal carbohydrate ingestion. Study design Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual, and intracerebroventricular catheters, electrocorticogram, and esophageal electromyogram electrodes and studied at 131±2 days' gestation. After a 2-hour baseline period, 10% sucrose was infused sublingually for the duration of the study. At 4 hours' time, NPY was injected into the fetal cerebral ventricles and fetal swallowing monitored for an additional 6 hours. Results During the basal period, mean (±SEM) swallowing averaged 0.8±0.1 swallows per minute. Fetal swallowing increased significantly in response to sublingual sucrose (1.3±0.1 swallows/min, P = .001), and further significantly increased at 4 to 6 hours after NPY injection into the cerebral ventricles (1.8±0.3, P = .001). Conclusion These results indicate central NPY stimulation of fetal ingestion beyond that resulting from sublingual 10% sucrose. The in utero development of NPY-induced ingestive behavior may be in preparation for high neonatal caloric intake.

Regulation of leptin expression in farm animals

Leptin is a hormone mainly expressed by adipose tissue (AT) in mammals and/or by liver in birds, at levels that differ according to genetic, physiological, nutritional and environmental factors, as well as hormone treatments (Houseknecht et al., 1998; Barb et al., 2002; Chilliard et al., 2002; Taouis et al., 2002).AT leptin mRNA level was higher in sheep and goat subcutaneous than visceral tissues, and the opposite was observed in cattle; it was higher in fat than in lean selection line in sheep. Leptin gene expression was decreased by undernutrition and increased by refeeding in AT of cattle and sheep, and decreased during fasting but not after feed restriction in AT of pig. In the chicken, both AT and liver leptin mRNA were decreased by undernutrition. In lactating goats, the replacement of part of the dietary concentrates by soybeans did not change leptin expression. The injection of NPY in sheep, as well as growth hormone (GH) treatment of growing sheep and cattle increased AT leptin mRNA. In the pig, AT leptin mRNA decreased after GH administration and estrogen-induced leptin mRNA increased with age and adiposity. In the chicken, estrogen treatment decreased AT and liver leptin mRNA. In vitro, insulin and glucocorticoïds increased AT leptin mRNA in cattle and pig, and leptin production in sheep. However, these effects on leptin gene expression were inhibited by GH. In the chicken, liver but not AT leptin mRNA was either increased by insulin, glucocorticoïds and GH or decreased by glucagon treatments. Long daylength increased AT lipogenic activities and leptin mRNA, as well as plasma leptin in sheep. In sheep, AT leptin mRNA increased from prebreeding to mid-pregnancy and declined to prebreeding levels during early lactation (Ehrhardt et al., 2001).

Leptin in ruminants. Gene expression in adipose tissue and mammary gland, and regulation of plasma concentration

This paper reviews data on leptin gene expression in adipose tissue (AT) and mammary gland of adult ruminants, as well as on plasma leptin variations, according to genetic, physiological, nutritional and environmental factors. AT leptin mRNA level was higher in sheep and goat subcutaneous than visceral tissues, and the opposite was observed in cattle; it was higher in fat than in lean selection line in sheep; it was decreased by undernutrition and increased by refeeding in cattle and sheep, and not changed by adding soybeans to the diet of lactating goats; it was increased by injection of NPY to sheep, and by GH treatment of growing sheep and cattle. Insulin and glucocorticoids in vitro increased AT leptin mRNA in cattle, and leptin production in sheep. Long daylength increased AT lipogenic activities and leptin mRNA, as well as plasma leptin in sheep. Mammary tissue leptin mRNA level was high during early pregnancy and was lower but still expressed during late pregnancy and lactation in sheep. Leptin was present in sheep mammary adipocytes, epithelial and myoepithelial cells during early pregnancy, late pregnancy and lactation, respectively. Plasma leptin in cattle and sheep was first studied thanks to a commercial “multi-species” kit. It was positively related to body fatness and energy balance or feeding level, and decreased by β-agonist injection. The recent development of specific RIA for ruminant leptin enabled more quantitative study of changes in plasma leptin concentration, which were explained for 35–50% by body fatness and for 15–20% by feeding level. The response of plasma leptin to meal intake was related positively to glycemia, and negatively to plasma 3-hydroxybutyrate. The putative physiological roles of changes in leptin gene expression are discussed in relation with published data on leptin receptors in several body tissues, and on in vivo or in vitro effects of leptin treatment.

Repeated inhibitory effects of NPY on hippocampal CA3 seizures and wet dog shakes

Intracerebroventricular injection of NPY inhibits epileptiform seizures and seizure-related “wet dog shakes” (WDS) following electrical stimulation of the dentate gyrus or subiculum. This study examined the effects of NPY on seizures and WDS elicited in hippocampal CA3. Like in the other hippocampal regions, NPY significantly inhibited both seizures and accompanying WDS consistent with in vitro data. The identification of an additional antiepileptic hippocampal target for NPY could prove therapeutically relevant considering that the hippocampal formation is a frequent seizure focus in human epilepsy. The effects of NPY were found to persist on seven repeated NPY injection days. Thus tolerance to the anti-seizure effects of NPY does not appear to develop rapidly. Tolerance being a problem with several current antiepileptic drugs, this further strengthens the concept of NPY receptors as a potential future antiepileptic target.

Neuropeptide Y and epilepsy: varying effects according to seizure type and receptor activation

In vitro and in vivo experiments suggest antiepileptic properties for NPY. In this study, the pharmacology of these effects was examined and compared in different rat models of seizures. Agonists for Y 1, Y 2 and Y 5 receptors reduced seizure-like activity in hippocampal cultures. Intracerebral injection of NPY or Y 5 agonists reduced the expression of focal seizures produced by a single electrical stimulation of the hippocampus. Conversely, NPY agonists increased the duration of generalized convulsive seizures induced by pentylenetetrazol. These results suggest that NPY reduces seizures of hippocampal origin through activation of Y 5 receptors. They also point to probable modulatory effects of NPY in brain structures other than the hippocampus, involved in initiation, propagation or control of seizures.

Neuropeptide Y in central control of feeding and interactions with orexin and leptin.

Neuropeptide (NPY) increases feeding when injected into the brain. In this study, we tested the hypothesis that its action might be related to feeding regulation of the orexin and leptin systems in rats. Intracerebroventricular administration of NPY (1 nmol/5 microL) stimulated feeding in rats. Injection of an antibody to orexin-A inhibited feeding, suggesting that endogenous orexin exerts a stimulatory tone on feeding. Intracerebroventricular injection of orexin antiserum before injection of NPY significantly attenuated the feeding response to NPY. On the other hand, ip pretreatment with leptin (2 mg/kg) significantly decreased food intake and inhibited NPY-induced feeding. We then examined whether orexin-containing neurons are activated under the stimulation of feeding in response to intracerebroventricular NPY or suppression of feeding in response to ip leptin, using Fos-like immunoreactivity (FLI) as a marker of neural activation. We observed that FLI was induced in the paraventricular, supraoptic, and dorsomedial nuclei as well as the lateral hypothalamic area (LHA) following administration of NPY. Double staining with anti-Fos and antiorexin antibodies revealed that 23.4% of the orexin-containing neurons in the LHA expressed FLI after NPY injection. Approximately 7.8% of the orexin-positive neurons in the LHA coexpressed Fos after leptin plus NPY. Our data indicate that a functional interaction among NPY, orexin, and leptin exists that may contribute to the central regulation of appetite.

The NPY Y1 receptor antagonist BIBP 3226 blocks NPY induced feeding via a non-specific mechanism

We have previously shown that intracerebroventricular BIBP 3226 inhibits NPY induced feeding in rats. However, this was associated with abnormal behaviour, likely to be due to interaction with Y1 receptors involved in mechanisms other than the control of food intake. In order to minimise such interactions we investigated the effects of paraventricular nucleus (PVN) injections of BIBP 3226 and its inactive enantiomer BIBP 3435. Intra-PVN injection of NPY (0.1–2.5 nmol/animal) increased food intake, with an EC 50 of approximately 0.15 nmol/animal. Injections of BIBP 3226 and BIBP 3435 (0.25–25 nmol) reduced NPY-induced food intake in a dose responsive manner, with BIBP 3226 reducing food intake by 95%, and BIBP 3435 by 65% at the highest dose tested. The reversibility of the effect of BIBP 3226 was investigated by measuring the feeding response to NPY (0.5 nmol) in animals 1 week after BIBP 3226 injection. The response to NPY was less in animals which had received high doses of BIBP 3226. Animals previously injected with saline vehicle alone showed a normal NPY feeding response. These results suggest that BIBP 3226 may be inhibiting NPY-induced food intake in a non-specific manner, not secondary to inhibition of the Y1 receptor. This does not, however rule out a role for the Y1 receptor in the control of food intake by NPY.

CART peptides in the central control of feeding and interactions with neuropeptide Y.

While CART peptides have been implicated as novel, putative peptide neurotransmitters/cotransmitters, behavioral effects of these peptides have not yet been demonstrated. In this study, we show the first behavioral effect of CART peptides. I.c.v. administration of CART peptide fragments inhibits feeding in rats. Moreover, injection of an antibody to CART peptide 82-103 stimulates feeding, suggesting that endogenous CART peptides exert an inhibitory tone on feeding. Injection of CART peptide 82-103 five min before NPY reduces the increase in feeding caused by injection of NPY alone. Also, in light microscopic immunohistochemical studies, NPY-positive varicosities were observed around CART peptide-positive cell bodies in the paraventricular nucleus of the hypothalamus. These data suggest functional interactions between CART peptides and NPY. These results indicate that CART peptides play a role in the control of food intake by the brain.

5-Hydroxytryptaminergic receptor agonists: effects on neuropeptide Y potentiation of feeding and respiratory quotient

The objective of the present report was to characterize further the potential interactive effects of NPY and 5-HT on feeding and whole-body calorimetry. Specifically, several experiments examined the impact of various 5-HT receptor agonists on NPY stimulated eating and alterations in respiratory quotient (RQ). This included the 5-HT 1A/1B receptor agonist RU 24969, the 5-HT 1B/2C agonist TFMPP and the 5-HT 2A/2C agonist DOI. In feeding tests conducted at the onset of the dark cycle, RU 24969, TFMPP and DOI were administered 5 min prior to PVN injection of NPY and food intake was measured 1 h postinjection. The metabolic effects of NPY following similar pretreatment were monitored using an open-circuit calorimeter measuring the volume of oxygen consumed (VO 2), carbon dioxide produced (VCO 2) and RQ (VCO 2/VO 2). PVN injection of NPY (50–100 pmol) potentiated feeding and evoked reliable increases in RQ. DOI (5–20 nmol), but not RU 24969 (5–20 nmol) or TFMPP (10–40 nmol), antagonized NPY induced eating and blocked the peptide's effects on RQ. These findings suggest that 5-HT 2A receptors within the PVN modulate NPY's effect on feeding and energy substrate utilization at the start of the nocturnal period.

Neuropeptide Y Produces Anxiety Via Y2-Type Receptors

Nakajima, M., A. Inui, A. Asakawa, K. Momose, N. Ueno, A. Teranishi, S. Baba and M. Kasuga. Neuropeptide Y produces anxiety via Y2-type receptors. Peptides 19(2) 359–363, 1998.—In the present study, the effects of intracerebroventricular (ICV) NPY, [Leu 31, Pro 34]NPY and NPY 13–36 have been evaluated with respect to anxiety in mice in the elevated plus maze. NPY had opposing effects on behavior, depending on the doses used. NPY decreased the normal preference for the closed arms of the maze at 0.7 nmol, indicating an anxiolytic effect; however, at 7 pmol NPY further increased the preference for the closed arm, indicating an anxiogenic effect. [Leu 31, Pro 34]NPY, a Y1-type receptor agonist, significantly reduced the preference for the closed arms at 70 pmol. NPY 13–36, a Y2-type receptor agonist, significantly intensified the preference at 20 pmol. It has been demonstrated that NPY produces not only an anxiolytic effect via Y1-type receptors, but also an anxiogenic effect via Y2-type receptors. The time course of these NPY actions are quite different and the anxiogenic effect was observed only shortly after ICV NPY injection.

Further investigations on the effects of neuropeptide Y on the secretion and growth of rat adrenal zona glomerulosa

NPY is a regulatory peptide, high levels of which are contained in adrenal glands of several mammals and which is co-released with catecholamines during various stressful conditions. The acute and chronic effects of NPY on adrenocortical secretion and growth were studied in the rat. NPY concentration-dependently increased aldosterone (ALDO), but not corticosterone (B) secretion of adrenal slices (maximal effective concentration was 10 −7 M). Two competitive inhibitors of NPY receptors, named PYX-1 and PYX-2, were found to dose-dependently inhibit ALDO response of adrenal preparations to 10 −7 M NPY; PYX-2 was more efficient than PYX-1, and at a concentration of 10 −5 M completely annulled the effect of 10 −7 M NPY. The acute bolus intraperitoneal (i.p.) injection of NPY (3 nmol/kg) raised plasma ALDO concentration (PAC), but not that of B (PBC); this effect of NPY was blocked by the simultaneous injection of PYX-2 (300 nmol/kg). The prolonged i.p. infusion with NPY (3 nmol/kg/h for 7 days) increased PAC (but not PBC) and induced a marked hypertrophy of the zona glomerulosa (ZG) and its parenchymal cells; dispersed ZG cells obtained from NPY-infused rats displayed a significantly enhanced basal and maximally agonist-stimulated ALDO production. The simultaneous infusion with PYX-2 (300 nmol/kg/h) completely annulled all these effects of NPY. The acute or chronic administration of PYX-2 alone did not evoke any apparent effect on the ZG secretion and growth. In light of these findings the following conclusions can be drawn: (i) NPY is able to stimulate not only the secretion, but also the growth of adrenal ZG in rats, via a receptor-mediated mechanism (since this effect is blocked by PYX-2); (ii) endogenous NPY does not play a prominent role in the physiological maintenance of secretion and growth of rat ZG (since PYX-2 alone is ineffective); (iii) NPY may play a crucial role in the fine tuning of the ZG functions in conditions requiring an increased release of mineralocorticoid hormones.

Differential effects of pertussis toxin on body temperature changes induced by neuropeptide Y and NPY 2–36

Many effects of NPY have been attributed to a decrease in the activity of adenylate cyclase. Pre-treatment with pertussis toxin (PTx) has been shown to inhibit many pharmacological effects of NPY including increased feeding following administration in the paraventricular nucleus (PVN). In the present study, we examined the influence of PTx pre-treatment on the effects of NPY on body temperature following administration in the preoptic area (POA), a region which seems to be the most sensitive to the effects of the peptide on body temperature. The effects of the same pre-treatment on the action of NPY 2–36 was also studied since we have found previously that this fragment produced opposite effects on body temperature to that of NPY when injected in the POA. PTx was administered 3 days prior to the injection of NPY or NPY 2–36. Results indicate that the hypothermic effect of NPY produced in the POA was blocked by PTx whereas the hyperthermic effect of NPY 2–36 was not affected. These results are important as they provide evidence that, in the POA at least, the receptors mediating the hypothermic effect of NPY might be biochemically different from those mediating the hyperthermic effect of NPY 2–36.

Desensitization by neuropeptide Y of effects of sympathetic stimulation on cardiac vagal action in anaesthetised dogs

The effects of a long-lasting intravenous infusion of neuropeptide Y (NPY, 180 ± 8 min, 53 ± 4 μg/kg/h) on the prolonged inhibition of cardiac vagal action evoked by cardiac sympathetic nerve stimulation and bolus intravenous injections of NPY were investigated in anaesthetised dogs. Sympathetic stimulation and NPY injection were performed on four separate occasions: once in control conditions, then once early and again late in the period of NPY infusion, and then on a final occasion 60–90 min after the cessation of NPY infusion. The maximum inhibition of cardiac vagal action evoked by an injection of NPY was significantly less late in the NPY infusion when compared with the other three injection groups (ANOVA, P < 0.001). Also the time to half-recovery of this response was significantly less than that seen in the other three injection groups (ANOVA, P < 0.001). The maximum inhibition of cardiac vagal action evoked by sympathetic stimulation was significantly reduced late in the NPY infusion when compared with the other three stimulation groups (ANOVA, P < 0.0001). The time for half-recovery of this response was also less than that of the other three stimulation groups (ANOVA, P < 0.001). The results indicate that desensitisation of the vagal attenuation to both exogenous NPY and sympathetic stimulation occurred during a long-lasting period of NPY infusion. This is consistent with the proposal that NPY is a mediator of this sympathetic-evoked vagal attenuation.

Intraventricular neuropeptide Y injections stimulate food intake in lean, but not obese Zucker rats

We examined the effect of acute third intraventricular (IVT) injections of either saline or NPY (0.95, 3.0, 9.5, or 30.0 μg in 1 μl) on the 1-, 4-, and 22-hour postinjection food and water intake of female obese (fa/fa), heterozygous lean (Fa/fa), and homozygous lean (Fa/Fa) Zucker rats. None of the doses of NPY had an effect on either food or water intake of fa/fa rats. A significant increase of food intake was seen in Fa/Fa rats at 1 and 4 hours after the 3.0 μg injection of NPY and at 1, 4, and 22 hours after the 9.5 μg injection of NPY. Both 3.0 and 9.5 μg of NPY also stimulated 1- and 4-hour postinjection food intake of Fa/fa rats, although this effect was significant only at 4 hours after the 3.0 μg dose. NPY had a less reliable effect on water intake; 3.0 μg of NPY stimulated 1-hour postinjection water intake of Fa/fa rats and 4-hour postinjection water intake of Fa/Fa rats. These results indicate that lean, but not obese Zucker rats, respond by eating more to centrally administered NPY. This deficit is similar to the effects seen with IVT insulin injections and may be a result of a common receptor-mediated mechanism.

NPY-induced inhibition of male copulatory activity is a direct behavioural effect

In adult, sexually-experienced male rats, the intracerebroventricular injection of NPY caused a dose-related inhibition of copulatory behaviour, all parameters (mount, intromission and ejaculation latencies, mount and intromission frequences, mean inter-intromission interval, post-ejaculatory interval) being significantly worsened at the dose of 8 μg/rat. Since rats were deprived of food during the behavioural test, it is concluded that inhibition of sexual behaviour is a ‘true’, direct behavioural effect of NPY, not due to a shift towards increased feeding.

Neuropeptide Y reduces ovarian blood flow in the rabbit

Neuropeptide Y-containing nerve fibers have previously been demonstrated to innervate the mammalian ovary. These nerve fibers innervate primarily the vasculature. In this study we have developed a method for in vivo measurement of the ovary blood flow rate by means of the 133Xe method. Using this technique we measured the ovary blood flow rate and investigated the dose-response relationship between close intraarterial-injected NPY and the ovary blood flow rate. A monoexponential washout curve for 133Xe was found for the whole washout process, ensuring that the blood flow rate at any time could be calculated from the curve. We found a mean blood flow rate in the nonpregnant rabbit ovary at 43.6±4.4 ml·(100 g) −1· min −1 (mean±SEM). Injection of NPY (20, 200, 2000 pM) in the aorta close to a. ovarica resulted in a dose-dependent decrease in the ovarian blood flow rate with a maximum reduction to 40.7±6.3% (mean±SEM) of the control blood flow rate. These findings make it likely that receptors able to interact with NPY are present in the vasculature of the rabbit ovary.