A receptor subtype involved in neuropeptide-Y-induced food intake

Gerald, Christophe; Walker, Mary W.; Criscione, Leoluca; Gustafson, Eric L.; Batzl‐Hartmann, Christine; Smith, Kip; Vaysse, Pierre J.‐J.; Durkin, Margaret M.; Laz, Thomas M.; Linemeyer, David L.; Schaffhauser, Andrea O.; Whitebread, Steven; Hofbauer, Karl G.; Taber, Robert I.; Branchek, Theresa A.; Weinshank, Richard L.

doi:10.1038/382168a0

Cited by 847 publications

(591 citation statements)

References 23 publications

Supporting

Mentioning

564

Contrasting

Unclassified

Order By: Relevance

“…NPY is a neurotransmitter widely expressed within the central and peripheral nervous systems affecting vasoconstriction, insulin secretion and food intake [7] [8]. NPY has also been demonstrated in islet cells and pancreatic nerve fibers [9].…”

Section: Introductionmentioning

confidence: 99%

Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy

Skärstrand

Dahlin

Lernmark

et al. 2013

Journal of Diabetes and its Complications

View full text Add to dashboard Cite

Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy. Link to publication Citation for published version (APA): Skärstrand, H., Dahlin, L. B., Lernmark, Å., & Vaziri Sani, F. (2013). Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy. Journal of Diabetes and its Complications, 27(6), 609-617. DOI: 10.1016/j.jdiacomp.2013 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Presented at meetingPresented in part as a poster at the 12 th Immunology of Diabetes Society (IDS) conference June [15][16][17][18][19] 2012 in Victoria, BC, Canada. Printed in the meeting abstract book on page 140. AbstractAims: The neurotransmitter Neuropeptide Y (NPY) was previously reported as a minor autoantigen in newly diagnosed type 1 diabetes (T1D) patients. The single nucleotide polymorphism at rs16139 (T1128C, L7P) in the NPY gene was associated with an increased risk for the development of type 2 diabetes (T2D). We aimed to develop a radiobinding assay for NPY-L (Leucine) and NPY-P (Proline) autoantibodies (A) to study the levels and the association with other islet autoantibodies and neuropathy. Methods: Autoantibodies against NPY-L, NPY-P, ZnT8, GAD65 and IA-2 were studied in T1D (n=48) and T2D (n=26) patients with duration up to 42 and 31 years. A subgroup of T1D (n=32) patients re-examined, 5-8 years after first visit, were tested for peripheral (Z-score) and autonomic neuropathy (E/I ratio). Results: NPY-LA and NPY-PA were detected in 23% and 19% in T1D (p<0.001), and 12% and 23% in T2D patients (p<0.001) compared to 2.5% controls (n=398). The levels of NPYA declined during follow-up in the T1D patients (p<0.001). The neuropathy was not related to the NPYA or the other islet autoantibodies. Conclusions: Regardless of the absence of an association between NPYA and neuropathy, NPY may contribute to the pathogenesis of T1D and T2D as a minor autoantigen.

show abstract

Section: Introductionmentioning

confidence: 99%

Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy

Skärstrand

Dahlin

Lernmark

et al. 2013

Journal of Diabetes and its Complications

View full text Add to dashboard Cite

show abstract

“…of feeding. [146][147][148][151][152][153][154][155] NPY neurons in the Arc may contribute to ORX's effects on food intake, as ORX neurons innervate this NPY neuronal population and stimulate it. 156 Presently, we will focus on the Y1-R, as accumulating evidence suggests that this Y-receptor subtype contributes to NPY action not only on consummatory behavior but also on emotional responses.…”

mentioning

confidence: 99%

Body weight is regulated by the brain: a link between feeding and emotion

2005

View full text Add to dashboard Cite

Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence. Maintaining energy homeostasis is fundamental for survival. However, obesity due to over-nutrition is an increasing worldwide public health problem. 1 In psychiatric practice, on the other hand, impaired appetite is one of the crucial issues. Anorexia and weight loss are common, for example, in patients suffering from depression. Eating disorders are medically intractable and life threatening. In addition, the so-called 'atypical' antipsychotic agents, currently and widely used to treat psychoses, often induce hyperphagia, obesity, and diabetes mellitus. [2][3][4] In the past decade, fortunately, there has been remarkable progress in understanding the molecular mechanisms of food intake and body weight. This is due in large part to increased research activity towards combating the rising incidences of obesity and associated metabolic disorders. As a result, it is now established that the central nervous system (CNS) senses and processes peripheral metabolic cues including leptin 5 and ghrelin, 6,7 resulting in coordinated energy homeostasis. However, the pathophysiology of the disequilibrium between energy intake and expenditure in psychiatric disorders remains largely unknown. Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to...

show abstract

“…Its wide range of action is exerted via several receptor subtypes, named Y 1 -[17±19], Y 2 -[20±22], Y 5 - [23] and y 6 - [24] receptor subtypes, whereas the related peptide PP binds to the Y 4 /PP 1 -receptor [25,26]. A putative Y 3 -receptor has been described only pharmacologically and no specific agonists or antagonists are known [27].…”

mentioning

confidence: 99%

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Söll

Dinger

Lundell

et al. 2001

European Journal of Biochemistry

View full text Add to dashboard Cite

In contrast, cyclo S±S [Cys20,Cys24]pNPY was found to be a highly selective ligand at the Y 2 -receptor, binding only threefold less efficiently than NPY. Analogues containing variations of positions 31 and 32 showed highly reduced affinity to the Y 1 -receptor, while binding to the Y 5 -receptor was affected less. Inhibition of cAMP-accumulation of selected peptides with replacements within position 20±23 of NPY showed preserved agonistic properties. The NPY analogues tested give insights into ligand±receptor interaction of NPY at the Y 1 -, Y 2 -and Y 5 -receptor and contribute to our understanding of subtype selectivity. Furthermore, the Y 1 -receptor-preferring peptides are novel tools that will provide insight into the physiological role of the Y 1 -receptor.Keywords: food intake; neuropeptides; NPY; selective ligands; structure±affinity relationship.Obesity, food intake and energy homeostasis are key areas of growing importance because obesity is beginning to replace malnutrition and infectious diseases as the most significant contributor to ill health in the developed world [1]. Neuropeptide Y (NPY) is one of the most important effector molecules of leptin: it is a key molecule in the regulation of food intake, it acts via several different receptor subtypes and elicits several physiological effects. Profound effects on stimulation of food intake, secretion of luteinizing and growth hormone, and insulin release suggest an important role for NPY in the pathophysiology of obesity and diabetes [2±5]. A wide range of other effects of NPY have been reported, such as potent vasoconstriction [6], facilitation of learning and memory [7], modulation of locomotor behaviours [8], induction of hypothermia [9,10], inhibition of sexual behaviour [11], shifts in circadian rhythms [12], modulation of cardiorespiratory parameters[13], anxiolytic potency [14] and inhibition of alcohol consumption and resistance [15].NPY is a 36-amino acid peptide amide belonging to the family of pancreatic polypeptides that includes also pancreatic polypeptide (PP) and peptide YY; it was first isolated from pig brain in 1982 [16].NPY is widely distributed within the central nervous system and in the periphery. [25,26]. A putative Y 3 -receptor has been described only pharmacologically and no specific agonists or antagonists are known [27]. All receptors belong to the G-protein coupled receptor superfamily [28]. The correlation of a certain receptor subtype to a distinct physiological effect is not yet fully understood. Recent studies even suggest that different receptor subtypes redundantly mediate identical actions in a given system, as has been shown for the Y 1 -and Y 5 -receptor in the regulation of food intake [3]. Findings that deficiencies in either the Y 1 -or the Y 5 -receptors do not significantly impair the normal feeding response to fasting or NPY stimulation, strongly indicate that both Y receptors are involved in appetite regulation by NPY [29,30]. Selective receptor agonists or antagonists are useful tools with which to stu...

show abstract

A receptor subtype involved in neuropeptide-Y-induced food intake

Cited by 847 publications

References 23 publications

Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy

Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy

Body weight is regulated by the brain: a link between feeding and emotion

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Contact Info

Product

Resources

About

A receptor subtype involved in neuropeptide-Y-induced food intake

Cited by 847 publications

References 23 publications

Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy

Neuropeptide Y autoantibodies in patients with long-term type 1 and type 2 diabetes and neuropathy

Body weight is regulated by the brain: a link between feeding and emotion

Novel analogues of neuropeptide Y with a preference for the Y1‐receptor

Contact Info

Product

Resources

About

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor