scholarly journals Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in CKD: translational opportunities and challenges

2021 ◽  
Author(s):  
Carmine Zoccali ◽  
Alberto Ortiz ◽  
Inga Arune Blumbyte ◽  
Sarina Rudolf ◽  
Annette G Beck-Sickinger ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Cardiovascular Events ◽  
Peptide Yy ◽  
Pharmaceutical Formulations ◽  
Renal Diseases ◽  
Dialysis Patients ◽  
Amino Acid Peptide ◽  
The Central Nervous System ◽  
Slow Progress ◽  
Expected Benefits

Abstract 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 the immune function. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of the gut-brain cross-talk. A progressive rise in circulating NPY accompanies the progression of CKD toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in the 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 a renewed research interest on the NPY system in psycho pharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health by drugs interfering with this system.

The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

2019 ◽  
Vol 20 (7) ◽  
pp. 750-758 ◽  
Author(s):  
Yi Wu ◽  
Hengxun He ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropeptide Y ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
Vital Role ◽  
Gut Peptides ◽  
Nonalcoholic Fatty Liver ◽  
The Central Nervous System

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

Neuropeptide Y induces fasted pattern of duodenal motility via Y2 receptors in conscious fed rats

2000 ◽  
Vol 278 (1) ◽  
pp. G32-G38 ◽  
Author(s):  
Mineko Fujimiya ◽  
Etsuro Itoh ◽  
Naoki Kihara ◽  
Ikuo Yamamoto ◽  
Masaki Fujimura ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Peptide Yy ◽  
Contractile Activity ◽  
Amino Acid Peptide ◽  
Duodenal Motility ◽  
Motor Activities ◽  
Manometric Method ◽  
Rat Duodenum ◽  
Freely Moving ◽  
The Brain

Neuropeptide Y (NPY), a 36-amino acid peptide abundantly expressed in the brain, has been implicated in the regulation of feeding and visceral functions. The present study was designed to investigate whether or not NPY specifically regulates duodenal motility. The manometric method was used to measure duodenal motility in conscious, freely moving rats. The rat duodenum showed phasic contractions mimicking the migrating motor complex in the fasted state that were replaced by irregular contractions after the ingestion of food. NPY powerfully affected the contractile activity after intracerebroventricular (icv) administration, changing fed (postprandial) patterns into phasic contractions characterized as fasted (interdigestive) patterns. This effect was mediated via receptors with pharmacological profiles similar to rat Y2and Y4 receptors, although neither Y1 nor Y5 agonists had any effects on motility despite potent feeding-stimulatory effects. Immunoneutralization with anti-NPY antiserum administered icv abolished fasted patterns and induced fed-like motor activities. An icv dose of peptide YY produced a different effect from NPY, with increase in the motor activities of both fed and fasted patterns. These results indicate that fasted and fed motor activities are regulated processes and that NPY induces fasted activity through Y2, and possibly Y4, receptors, which may represent an integrated mechanism linked to the onset of feeding behavior.

Abnormal levels of neuropeptide Y and peptide YY in colon in the irritable bowel syndrome (IBS)

2001 ◽  
Vol 120 (5) ◽  
pp. A753-A754
Author(s):  
M SIMREN ◽  
G RINGSTROM ◽  
P STOTZER ◽  
H ABRAHAMSSON ◽  
E BJOMSSON
Keyword(s):  
Irritable Bowel Syndrome ◽  
Neuropeptide Y ◽  
Peptide Yy ◽  
Irritable Bowel

Identification of cultured cells selectively expressing Y1-, Y2-, or Y3-type receptors for neuropeptide Y/peptide YY

Life Sciences ◽  
1992 ◽  
Vol 50 (4) ◽  
pp. PL7-PL12 ◽  
Author(s):  
Claes Wahlestedt ◽  
S. Regunathan ◽  
Donald J. Reis
Keyword(s):  
Neuropeptide Y ◽  
Cultured Cells ◽  
Peptide Yy

Diet-derived nutrients mediate the inhibition of hypothalamic NPY neurons in the arcuate nucleus of mice during refeeding

2009 ◽  
Vol 297 (1) ◽  
pp. R100-R110 ◽  
Author(s):  
Csilla Becskei ◽  
Thomas A. Lutz ◽  
Thomas Riediger
Keyword(s):  
Neuropeptide Y ◽  
Arcuate Nucleus ◽  
Peptide Yy ◽  
Small Reduction ◽  
Hypothalamic Arcuate Nucleus ◽  
Ad Libitum ◽  
Fos Expression

Fasting activates orexigenic neuropeptide Y neurons in the hypothalamic arcuate nucleus (ARC) of mice, which is reversed by 2 h refeeding with standard chow. Here, we investigated the contribution of diet-derived macronutrients and anorectic hormones to the reversal of the fasting-induced ARC activation during 2 h refeeding. Refeeding of 12-h-fasted mice with a cellulose-based, noncaloric mash induced only a small reduction in c-Fos expression. Refeeding with diets, containing carbohydrates, protein, or fat alone reversed it similar to chow; however, this effect depended on the amount of intake. The fasting-induced ARC activation was unchanged by subcutaneously injected amylin, CCK (both 20 μg/kg), insulin (0.2 U/kg and 0.05 U/kg) or leptin (2.6 mg/kg). Insulin and leptin had no effect on c-Fos expression in neuropeptide Y or proopiomelanocortin-containing ARC neurons. Interestingly, CCK but not amylin reduced the ghrelin-induced c-Fos expression in the ARC in ad libitum-fed mice, suggesting that CCK may inhibit orexigenic ARC neurons when acting together with other feeding-related signals. We conclude that all three macronutrients and also non-nutritive, ingestion-dependent signals contribute to an inhibition of orexigenic ARC neurons after refeeding. Similar to the previously demonstrated inhibitory in vivo action of peptide YY, CCK may be a postprandial mediator of ARC inhibition.

Multi-organ coordination of lipoprotein secretion by hormones, nutrients and neural networks

2021 ◽  
Author(s):  
Priska Stahel ◽  
Changing Xiao ◽  
Avital Nahmias ◽  
Lili Tian ◽  
Gary Franklin Lewis
Keyword(s):  
Neural Networks ◽  
Adipose Tissue ◽  
Peptide Yy ◽  
Atherosclerotic Cardiovascular Disease ◽  
Neural Signals ◽  
Nutritional Factors ◽  
Lipoprotein Secretion ◽  
The Central Nervous System ◽  
Regulatory Effects ◽  
The Brain

Abstract Plasma triglyceride-rich lipoproteins (TRL), particularly atherogenic remnant lipoproteins, contribute to atherosclerotic cardiovascular disease (ASCVD). Hypertriglyceridemia may arise in part from hypersecretion of TRLs by the liver and intestine. Here we focus on the complex network of hormonal, nutritional, and neuronal interorgan communication that regulates secretion of TRLs, and provide our perspective on the relative importance of these factors. Hormones and peptides originating from the pancreas (insulin, glucagon), gut (GLP-1, GLP-2, ghrelin, CCK, peptide YY), adipose tissue (leptin, adiponectin) and brain (GLP-1) modulate TRL secretion by receptor-mediated responses and indirectly via neural networks. In addition, the gut microbiome and bile acids influence lipoprotein secretion in humans and animal models. Several nutritional factors modulate hepatic lipoprotein secretion through effects on the central nervous system. Vagal afferent signalling from the gut to the brain and efferent signals from the brain to the liver and gut are modulated by hormonal and nutritional factors to influence TRL secretion. Some of these factors have been extensively studied and shown to have robust regulatory effects whereas others are ‘emerging’ regulators, whose significance remains to be determined. The quantitative importance of these factors relative to one another and relative to the key regulatory role of lipid availability remains largely unknown. Our understanding of the complex interorgan regulation of TRL secretion is rapidly evolving to appreciate the extensive hormonal, nutritional and neural signals emanating not only from gut and liver but also from the brain, pancreas, and adipose tissue.

Dexamethasone rapidly increases hypothalamic neuropeptide Y secretion in adrenalectomized ob/ob mice

1996 ◽  
Vol 271 (1) ◽  
pp. E151-E158 ◽  
Author(s):  
H. L. Chen ◽  
D. R. Romsos
Keyword(s):  
Neuropeptide Y ◽  
Arcuate Nucleus ◽  
Rapid Onset ◽  
Brown Adipose ◽  
Specific Enhancement ◽  
Brown Adipose Tissue Thermogenesis ◽  
The Central Nervous System ◽  
Rapid Transport ◽  
The Brain

A single intracerebroventricular injection of dexamethasone (DEX) rapidly (within 30 min) suppresses brown adipose tissue thermogenesis and increases plasma insulin concentrations in adrenal-ectomized (ADX) ob/ob mice but not in ADX lean mice. Intracerebroventricular neuropeptide Y (NPY) administered intracerebroventricularly causes these same metabolic changes within 30 min in both ob/ob and lean ADX mice. We therefore hypothesized that DEX exerts these rapid-onset metabolic actions in ob/ob mice via a phenotype-specific enhancement of NPY secretion within the central nervous system. In support of this hypothesis, DEX (a type II glucocorticoid receptor agonist) administered intracerebroventricularly selectively lowered NPY concentrations in the whole hypothalamus of ADX ob/ob mice by 35% and in the arcuate nucleus region by approximately 70% within 30 min but not in the brain stem or hippocampus or in any of these regions of lean mice. DEX also functioned in vitro to enhance depolarization-dependent release of NPY from hypothalamic blocks of ADX ob/ob mice but not of ADX lean mice. Thus DEX acts in the hypothalamus of ob/ob mice in a phenotype-specific manner to evoke rapid transport of NPY from cell bodies within the arcuate nucleus to terminal regions including the dorsomedial and ventromedial hypothalamic regions for release.

Neuropeptide Y inhibits estrous behavior and stimulates feeding via separate receptors in Syrian hamsters

2001 ◽  
Vol 280 (4) ◽  
pp. R1061-R1068 ◽  
Author(s):  
Eric S. Corp ◽  
Beatrice Gréco ◽  
J. Bradley Powers ◽  
Carrie L. Marín Bivens ◽  
George N. Wade
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Feeding Behavior ◽  
Sexual Behaviors ◽  
Peptide Yy ◽  
Receptor Subtypes ◽  
Syrian Hamsters ◽  
Total Food Intake ◽  
Npy Receptor ◽  
Estrous Behavior

Central injections of neuropeptide Y (NPY) increase food intake in Syrian hamsters; however, the effect of NPY on sexual behavior in hamsters is not known nor are the receptor subtypes involved in feeding and sexual behaviors. We demonstrate that NPY inhibits lordosis duration in a dose-related fashion after lateral ventricular injection in ovariectomized, steroid-primed Syrian hamsters. Under the same conditions, we compared the effect of two receptor-differentiating agonists derived from peptide YY (PYY), PYY-(3–36) and [Leu31,Pro34]PYY, on lordosis duration and food intake. PYY-(3–36) produced a 91% reduction in lordosis duration at 0.24 nmol. [Leu31,Pro34]PYY was less potent, producing a reduction in lordosis duration (66%) only at 2.4 nmol. These results suggest NPY effects on estrous behavior are principally mediated by Y2 receptors. PYY-(3–36) and [Leu31,Pro34]PYY stimulated comparable dose-related increases in total food intake (2 h), suggesting Y5 receptors are involved in feeding. The significance of different NPY receptor subtypes controlling estrous and feeding behavior is highlighted by results on expression of Fos immunoreactivity (Fos-IR) elicited by either PYY-(3–36) or [Leu31,Pro34]PYY at a dose of each that differentiated between the two behaviors. Some differences were seen in the distribution of Fos-IR produced by the two peptides. Overall, however, the patterns of expression were similar. Our behavioral and anatomic results suggest that NPY-containing pathways controlling estrous and feeding behavior innervate similar nuclei, with the divergence in pathways controlling the separate behaviors characterized by linkage to different NPY receptor subtypes.

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