Y-receptor subtypes—how many more?

Blomqvist, Anders; Herzog, Herbert

doi:10.1016/s0166-2236(96)01057-0

Cited by 496 publications

(268 citation statements)

References 53 publications

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“…Neuropeptide Y (NPY) is a recently identified osteo-neuromodulator shown to regulate bone cell function [7] and [8]. NPY is a neurotransmitter widely expressed through the peripheral and central nervous system, and its actions are mediated through the activation of G-protein coupled receptors, namely Y1, Y2, Y4, Y5 and y6 receptors [9]. Through specific activation of the Y1 receptor, NPY has been shown to play a critical role in a number of centrally-regulated physiological functions, such as energy homeostasis [10], anxiety [11], cardiovascular function [12] and neurogenesis [13].…”

Section: Introductionmentioning

confidence: 99%

Neuropeptide Y Y1 receptor antagonism increases bone mass in mice

Sousa

Baldock

Enriquez

et al. 2012

Bone

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The neuropeptide Y system has emerged as one of the major neural signalling pathways regulating bone homeostasis. Absence of Y1 receptor signalling from bone forming osteoblasts is responsible for an enhancement on bone mass in mice, suggesting that pharmacological blockade of Y1 receptors may offer a novel anabolic treatment option for improving bone mass. Here we show that oral administration of the selective Y1 receptor antagonist BIBO3304 for 8 weeks dose-dependently increases bone mass in mice. Histomorphometric analysis revealed a significant 1.5-fold increase in cancellous bone volume in the femora of mice treated with BIBO3304. Furthermore, bone microarchitecture was improved, with greater trabecular number and trabecular thickness. This increase in bone mass was associated with a significant increase in bone anabolic activity of osteoblasts and, interestingly, was evident despite a coincident increase in bone resorption, as evidenced by an increase in the number of the osteolytic osteoclasts. Changes were also evident in cortical bone, with a significant increase in periosteal mineral apposition rate. Importantly, no adverse extra-skeletal side effects were observed through Y1 receptor antagonism over the 8-week treatment period, with no effects of even the higher BIBO3304 dose on body weight, adiposity, energy metabolism or circulating corticosterone levels. Taken together, this work describes the first NPY-based anabolic treatment for improving bone mass, and highlights the therapeutic potential of blocking Y1 receptor signalling for the prevention of, or recovery from, degenerative skeletal diseases.

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Section: Introductionmentioning

confidence: 99%

Neuropeptide Y Y1 receptor antagonism increases bone mass in mice

Sousa

Baldock

Enriquez

et al. 2012

Bone

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“…One of these hormones is peptide YY (PYY), which belongs to a family of peptides including neuropeptide Y (NPY) and pancreatic polypeptide (PP), all of which are known to have potent effects on feeding and energy balance via their unique interactions with G-protein-coupled Y receptors (Y1, Y2, Y4, Y5, y6) (Blomqvist and Herzog, 1997, Stanley et al, 1986and Ueno et al, 1999.…”

Section: Introductionmentioning

confidence: 99%

“…Two forms of PYY exist in the circulation: the full length PYY1-36, and the shortened form PYY3-36, cleaved from secreted PYY1-36 by the cell surface enzyme dipeptidyl peptidase IV (Lundberg et al, 1982). PYY1-36 binds to all known Y receptors, albeit to each with differing affinities, whereas PYY3-36 preferentially binds the Y2 receptor and to a lesser extent the Y5 receptor (Blomqvist and Herzog, 1997). Obese subjects have significantly reduced circulating levels of PYY (Batterham et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

PYY transgenic mice are protected against diet-induced and genetic obesity

et al. 2008

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The gut-derived hormone, peptide YY (PYY) reduces food intake and enhances satiety in both humans and animals. Obese individuals also have a deficiency in circulating peptide YY, although whether this is a cause or a consequence of obesity is unclear. Our aims were to determine whether peptide YY (PYY) over-expression may have therapeutic effects for the treatment of obesity by altering energy balance and glucose homeostasis. We generated PYY transgenic mice and measured body weight, food intake, temperature, adiposity, glucose tolerance, circulating hormone and lipid concentrations and hypothalamic neuropeptide levels (neuropeptide Y; proopiomelanocortin, and thyrotropin-releasing hormone) under chow and high-fat feeding and after crossing these mice onto the genetically obese leptin-deficient ob/ob mouse background. PYY transgenic mice were protected against diet-induced obesity in association with increased body temperature (indicative of increased thermogenesis) and sustained expression of thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus. Moreover, PYY transgenic mice crossed onto the genetically obese ob/ob background had significantly decreased weight gain and adiposity, reduced serum triglyceride levels and improved glucose tolerance compared to ob/ob controls. There was no effect of PYY transgenic over expression on basal or fastinginduced food intake measured at 11-12 weeks of age. Together, these findings suggest that long-term administration of PYY, PYY-like compounds or agents that stimulate PYY synthesis in vivo can reduce excess adiposity and improve glucose tolerance, possibly via effects on the hypothalamo-pituitary-thyroid axis and thermogenesis.

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“…[146][147][148] NPY also affects endocrine/autonomic responses, seizures, and anxiety. [146][147][148] NPY neurons are distributed in many CNS sites, including the Arc. 149,150 Importantly, NPY-producing Arc neurons coexpress AgRP and are inhibited by leptin.…”

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confidence: 99%

“…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.…”

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confidence: 99%

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

2005

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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...

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Y-receptor subtypes—how many more?

Cited by 496 publications

References 53 publications

Neuropeptide Y Y1 receptor antagonism increases bone mass in mice

Neuropeptide Y Y1 receptor antagonism increases bone mass in mice

PYY transgenic mice are protected against diet-induced and genetic obesity

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

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