Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system.

• MeSH
• chronická renální insuficience * komplikace   terapie   MeSH
• dialýza ledvin MeSH
• kognitivní dysfunkce * etiologie   MeSH
• lidé MeSH
• neuropeptid Y MeSH
• receptory neuropeptidu Y MeSH
• renální hypertenze * MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Článek představuje studii účinku modifikovaného fragmentu neuropeptidu Y (HL-Ile-L-Asn-L-Leu-L-Nle- L-Ser-L-Arg-L-Asn-L-Arg-L-Tyr-NH2) zvaného nonapeptid NP9 na paměťové fáze a extrapolační únikový test zvířat. Studie byla provedena v testu pasivního vyhýbání s intaktními zvířaty a zvířaty ošetřeným skopolaminem a v extrapolačním únikovém testu. NP9 byl zkoumán v rozmezí dávek 0,04–0,4 mg/kg při jednorázovém intranazálním podání. Srovnávaným léčivem byl peptidový nootropní lék Semax® (Met-Glu-His-Phe-Pro-Gly-Pro) v dávce 0,1 mg/kg. Účinnost byla hodnocena podle retenční latence, procenta zvířat, která dosáhla kritéria učení, počtu neúplných pokusů o vstup, indexu antiamnestické aktivity vypočítaného Butlerovým vzorcem a počtu zvířat, která úspěšně provedla extrapolační únikový test. NP9 u většiny parametrů překonal přípravek Semax®. Ukázal schopnost zlepšit zapamatování ovlivněním I. paměťové fáze, a pokud byl NP9 podán po stresovém stimulu, usnadnil útlum negativních zkušeností. Také zvýšil kognitivní schopnosti zvířat v podmínkách averzního prostředí při extrapolačním únikovém testu. Peptid NP9 je tedy slibným potenciálním léčivem pro léčbu kognitivních poruch a posttraumatické stresové poruchy, vhodným pro další výzkum.

The article presents a study of the effect of a modified fragment of neuropeptide Y (H-L-Ile-L-Asn-L-Leu-L-Nle-L-Ser- L-Arg-L-Asn-L-Arg-L-Tyr-NH2) named nonapeptide NP9 on the memory phases and extrapolation escape of animals. The study was performed in the passive avoidance test with intact animals, scopolamine-treated animals, and the extrapolation escape task. NP9 was investigated in the dose range of 0.04–0.4 mg/kg with a single intranasal administration. The comparison drug used peptide nootropic medicine Semax® (Met-Glu-His-Phe-Pro-Gly-Pro) at a dose of 0.1 mg/kg. Efficiency was assessed by the retention latency, the percentage of animals that have reached the learning criterion, the number of incomplete attempts to enter, the antiamnestic activity index calculated by Butler’s formula, and the number of animals that successfully performed the extrapolation escape task. Peptide NP9 was superior to Semax® in most indicators. It demonstrated the ability to improve memorization due to its effect on I phase of memory and facilitated extinction of negative experiences when administered after a stress stimulus. NP9 also increased the cognitive ability of animals in the conditions an aversive environment in the extrapolation escape test. Thus, peptide NP9 is promising for a further study as a potential drug for the treatment of cognitive impairment and therapy of post-traumatic stress disorder.

• Klíčová slova
• test pasivního vyhýbání, paměťové fáze, extrapolovaný únikový úkol,
• MeSH
• myši MeSH
• neuropeptid Y * terapeutické užití   MeSH
• paměť * účinky léků   MeSH
• testy paměti a učení MeSH
• výzkum MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.

• MeSH
• autoprotilátky * MeSH
• ghrelin imunologie   MeSH
• inzulin imunologie   MeSH
• leptin imunologie   MeSH
• lidé MeSH
• melanocyty stimulující hormony imunologie   MeSH
• neuropeptid Y imunologie   MeSH
• poruchy příjmu potravy imunologie   mikrobiologie   MeSH
• střevní mikroflóra imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Increased activity of the sympathetic nervous system (SNS) has been proposed as a risk factor for increased cardiovascular mortality in patients with chronic kidney disease (CKD). Information on the activity of cardiac sympathetic innervation is non-homogeneous and incomplete. The aim of our study was to evaluate the tonic effect of SNS on heart rate, norepinephrine turnover and direct and indirect effects of norepinephrine in left ventricles of subtotally nephrectomized rats (SNX) in comparison with sham-operated animals (SHAM). Renal failure was verified by measuring serum creatinine and urea levels. SNX rats developed increased heart rates and blood pressure (BP). The increase in heart rate was not caused by sympathetic overactivity as the negative chronotropic effect of metipranolol did not differ between the SNX and SHAM animals. The positive inotropic effects of norepinephrine and tyramine on papillary muscle were not significantly different. Norepinephrine turnover was measured after the administration of tyrosine hydroxylase inhibitor, pargyline, tyramine, desipramine, and KCl induced depolarization. The absolute amount of released norepinephrine was comparable in both groups despite a significantly decreased norepinephrine concentration in the cardiac tissue of the SNX rats. We conclude that CKD associated with renal denervation in rats led to adaptive changes characterized by an increased reuptake and intracellular norepinephrine turnover which maintained normal reactivity of the heart to sympathetic stimulation.

• MeSH
• chronická renální insuficience komplikace   metabolismus   patofyziologie   MeSH
• kardiovaskulární nemoci etiologie   MeSH
• ledviny metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nefrektomie MeSH
• neuropeptid Y metabolismus   MeSH
• noradrenalin krev   MeSH
• peptid spojený s genem pro kalcitonin metabolismus   MeSH
• potkani Wistar MeSH
• srdeční frekvence MeSH
• srdeční komory metabolismus   patofyziologie   MeSH
• sympatický nervový systém patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• galanin fyziologie   MeSH
• gastrointestinální hormony fyziologie   MeSH
• hormon uvolňující gonadotropiny analýza   metabolismus   MeSH
• hormon uvolňující kortikotropin analýza   metabolismus   MeSH
• hypothalamus fyziologie   metabolismus   MeSH
• inzulin fyziologie   metabolismus   MeSH
• leptin analýza   metabolismus   MeSH
• lidé MeSH
• mentální anorexie metabolismus   patofyziologie   MeSH
• neuropeptid Y fyziologie   MeSH
• neurosekreční systémy fyziologie   patofyziologie   MeSH
• obezita etiologie   metabolismus   patofyziologie   MeSH
• orexiny fyziologie   metabolismus   MeSH
• poruchy příjmu potravy etiologie   metabolismus   patofyziologie   MeSH
• regulace chuti k jídlu fyziologie   MeSH
• systém hypotalamus-hypofýza patofyziologie   MeSH
• tuková tkáň chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasis are not fully understood. METHODS & RESULTS: Here we show adipocyte DNL controls crosstalk to localized sympathetic neurons that mediate expansion of beige/brite adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes (UCP1-FASNKO mice) cause these effects in iWAT. CONCLUSIONS: These results demonstrate that downregulation of fatty acid synthesis via FASN depletion in white adipocytes of mature mice can stimulate neuronal signaling to control thermogenic programming in iWAT.

• MeSH
• AMP cyklický metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• kultivované buňky MeSH
• lipogeneze * MeSH
• mastné kyseliny biosyntéza   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neurony metabolismus   fyziologie   MeSH
• neuropeptid Y metabolismus   MeSH
• sympatický nervový systém cytologie   fyziologie   MeSH
• syntázy mastných kyselin metabolismus   MeSH
• termogeneze * MeSH
• tukové buňky metabolismus   MeSH
• tyrosin-3-monooxygenasa metabolismus   MeSH
• uncoupling protein 1 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH

This study tested the hypothesis that neuropeptide Y (NPY) and NPY receptors 1 (Y1) and 2 (Y2) participate in lung allograft rejection. Inflammation in grafts may include interaction between blood leukocytes and graft endothelial cells and marked accumulation of intravascular blood leukocytes. Fewer leukocytes accumulate in lung than in kidney allografts. Lung transplantion was performed in the Dark Agouti to Lewis rat strain combination. Intravascular and intraalveolar leukocytes were isolated from the grafts, and we evaluated the mRNA expression of NPY, Y1, and Y2 by real-time RT-PCR as well as the peptide expression of NPY by radioimmunoassay and immunohistochemistry. NPY and Y1 were expressed by pulmonary intravascular and intraalveolar leukocytes. Y1 was up-regulated by pulmonary intravascular and intraalveolar leukocytes during allograft rejection while Y2 could not be detected. Higher NPY expression levels in intravascular leukocytes were observed in lung compared to kidney allografts, which were investigated previously. Our findings suggest that an increased leukocytic expression of NPY in lung compared to kidney allografts results in a reduced accumulation of leukocytes in allograft vessels.

• MeSH
• akutní nemoc MeSH
• alografty MeSH
• krysa rodu rattus MeSH
• leukocyty imunologie   patologie   MeSH
• neuropeptid Y imunologie   MeSH
• plíce imunologie   patologie   MeSH
• potkani inbrední LEW MeSH
• receptory neuropeptidu Y imunologie   MeSH
• receptory neuropeptidů imunologie   MeSH
• receptory spřažené s G-proteiny imunologie   MeSH
• regulace genové exprese imunologie   MeSH
• rejekce štěpu imunologie   patologie   MeSH
• transplantace plic * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The changes in gastrointestinal hormones associated with pancreatic ductal adenocarcinoma (PDAC) in patients with impaired glucoregulation have yet to be evaluated. The aim of this study was to determine plasma concentrations of selected gastrointestinal hormones in PDAC patients with and without diabetes and to compare them with levels found in Type 2 diabetic patients without cancer. METHODS: In this study we examined plasma concentrations of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide 1 (GLP-1), pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY), and cytokines leptin and adiponectin in 94 patients with histologically confirmed PDAC. Thirty-nine patients with Type 2 diabetes without PDAC and 29 healthy individuals with no evidence of acute or chronic diseases were examined as controls. RESULTS: Significantly lower plasma concentrations of GIP were found in PDAC patients with new-onset diabetes/prediabetes (n = 76), or in those with normal glucose regulation (n = 18), compared to patients with Type 2 diabetes without PDAC and controls (15.5 (3.7-64.5) or 6.5 (1.7-24.5) vs. 39.8 (15.1-104.7) and 28.8 (7.4-112.2) ng/L, p < 0.001); the same relationship was observed for PP (38.9 (10.2-147.9) or 28.1 (7.9-100.0) vs 89.1 (38.0-208.9) and 75.8 (30.1-190.6) ng/L, p < 0.01), respectively. The lowest levels of GIP and PP concentrations were found in PDAC patients with new-onset diabetes/prediabetes and weight loss > 2 kg (p < 0.001). CONCLUSIONS: We conclude that GIP and PP plasma concentrations are lower in pancreatic cancer irrespective of the degree of glucose intolerance as compared to Type 2 diabetic patients and healthy controls. In new onset diabetes especially if associated with weight loss, these changes may represent a new clue for the diagnosis of PDAC.

• MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu krev   komplikace   patofyziologie   MeSH
• dospělí MeSH
• duktální karcinom pankreatu krev   komplikace   diagnóza   patofyziologie   MeSH
• glukagonu podobný peptid 1 krev   MeSH
• hmotnostní úbytek * MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory slinivky břišní krev   komplikace   diagnóza   patofyziologie   MeSH
• neuropeptid Y krev   MeSH
• pankreatický polypeptid krev   MeSH
• peptid YY krev   MeSH
• porucha glukózové tolerance krev   komplikace   patofyziologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• žaludeční inhibiční polypeptid krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Leptin down-regulates orexigenic and up-regulates anorexigenic neuropeptide gene expression in hypothalamus. Surgical removal of adipose tissue leads to decrease in circulating leptin concentrations in rats. In the present study, we tested: (a) regulation of neuropeptide gene expression in hypothalamus, (b) food intake, and (c) standard growth rate after removal of adipose tissue in rats. Partial lipectomy caused an approximately 10-fold reduction of subcutaneous, retroperitoneal and epididymal adipose tissue weight (at the end of experiments adipose tissue weight was 1.5 ± 0.9 in lipectomy and 15 ± 3.9 g in control rats; statistically significant). Compared to control rats, the animals subjected to lipectomy presented increased food intake, standard growth rate, and decreased serum leptin concentrations (2.6 ± 0.8 vs. 3.7 ± 1.2 ng/mL in the controls, statistically significant). These changes were associated with approximately twofold increase in neuropeptide Y, threefold increase in agouti-related peptide (orexigenic neuropeptides) and about 50% decrease in pro-opiomelanocortin and cocaine–amphetamine-regulated transcript peptide (anorexigenic neuropeptides) mRNA levels in the hypothalamus. These results suggest that partial lipectomy, leading to a decrease in circulating leptin concentrations, may exert an effect on hypothalamic orexigenic and anorexigenic neuropeptide gene expression, and consequently modulate food intake and standard growth rate in rats.

• MeSH
• AGRP protein genetika   izolace a purifikace   metabolismus   MeSH
• bílá tuková tkáň chirurgie   metabolismus   účinky léků   MeSH
• biomedicínský výzkum metody   trendy   MeSH
• experimenty na zvířatech MeSH
• hypothalamus * účinky léků   zranění   MeSH
• kokain analogy a deriváty   izolace a purifikace   MeSH
• leptin izolace a purifikace   krev   MeSH
• lipektomie * metody   využití   MeSH
• neuropeptid Y genetika   metabolismus   MeSH
• peptidové hormony genetika   izolace a purifikace   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   využití   MeSH
• potkani Wistar MeSH
• pro-opiomelanokortin genetika   izolace a purifikace   metabolismus   MeSH
• regulace genové exprese * fyziologie   genetika   účinky léků   MeSH
• statistika jako téma MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• biologický transport MeSH
• biomechanika fyziologie   MeSH
• centrální nervový systém fyziologie   MeSH
• cytoplazma fyziologie   MeSH
• kardiomyocyty * fyziologie   MeSH
• kontrakce myokardu * fyziologie   MeSH
• lidé MeSH
• neuropeptid Y fyziologie   MeSH
• sarkoplazmatické retikulum fyziologie   MeSH
• srdce fyziologie   MeSH
• svalové buňky fyziologie   MeSH
• vápník fyziologie   MeSH
• vápníkové kanály - typ L fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH