Journal ArticleDOI
Prader-Willi syndrome: A model for understanding the ghrelin system.
Maithé Tauber,Maithé Tauber,Muriel Coupaye,Gwenaelle Diene,Catherine Molinas,Catherine Molinas,Marion Valette,Véronique Beauloye +7 more
TLDR
The current view of Prader‐Willi syndrome is presented, its natural history is explained, and recent data on the ghrelin system in PWS patients are discussed, to discuss the therapeutic approach of modulating the gh Relins system in these patients and the first promising results.Abstract:
Subsequent to the discovery of ghrelin as the endogenous ligand of growth hormone secretagogue receptor 1a, this unique gut peptide has been found to exert numerous physiological effects, such as appetite stimulation and lipid accumulation via the central regulating mechanisms in the hypothalamus, stimulation of gastric motility, regulation of glucose metabolism and brown fat thermogenesis, and modulation of stress, anxiety, taste sensation, reward-seeking behaviour and the sleep/wake cycle. Prader-Willi syndrome (PWS) has been described as a unique pathological state characterised by severe obesity and high circulating levels of ghrelin. It was hypothesised that hyperghrelinaemia would explain at least a part of the feeding behaviour and body composition of PWS patients, who are characterised by hyperphagia, an obsession with food and food-seeking, and increased adiposity. Initially, the link between hyperghrelinaemia and growth hormone deficiency, which is observed in 90% of the children with PWS, was not fully understood. Over the years, however, the increasing knowledge on ghrelin, PWS features and the natural history of the disease has led to a more comprehensive description of the abnormal ghrelin system and its role in the pathophysiology of this rare and complex neurodevelopmental genetic disease. In the present study, we (a) present the current view of PWS; (b) explain its natural history, including recent data on the ghrelin system in PWS patients; and (c) discuss the therapeutic approach of modulating the ghrelin system in these patients and the first promising results.read more
Citations
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Ghrelin degradation by serum and tissue homogenates: identification of the cleavage sites
Carine De Vriese,Françoise Grégoire,Roger Lema Kisoka,Magali Waelbroeck,Patrick Robberecht,Christine Delporte +5 more
TL;DR: In this paper, the degradation of ghrelin by rat and human serum, purified commercial enzymes, and tissues homogenates was analyzed by combining HPLC and mass spectrometry.
Journal ArticleDOI
Endocrine disorders in Prader-Willi syndrome: a model to understand and treat hypothalamic dysfunction.
Maithé Tauber,Charlotte Höybye +1 more
TL;DR: A review of the accumulated knowledge on genetics, pathophysiology, and treatment approaches of Prader-Willi syndrome can be found in this article, where a model of hypothalamic dysfunction is discussed.
Journal ArticleDOI
Obesity in Prader–Willi syndrome: physiopathological mechanisms, nutritional and pharmacological approaches
Giovanna Muscogiuri,Luigi Barrea,F. Faggiano,Maria Ida Maiorino,M. Parrillo,G. Pugliese,R. Ruggeri,Elisabetta Scarano,Silvia Savastano,A. Colao,Restare +10 more
TL;DR: A review of the current evidence on obesity and PWS, covering physiopathological aspects, obesity-related complications and conservative management is provided in this paper, where three main genetic subtypes are represented by paternal 15q11-q13 deletion, maternal uniparental disomy 15, and imprinting defect.
Journal ArticleDOI
Update on Diabetes Mellitus and Glucose Metabolism Alterations in Prader-Willi Syndrome.
Antonino Crinò,Graziano Grugni +1 more
TL;DR: Early intervention to prevent obesity and the regular monitoring of glucose levels are recommended in PWS subjects, however, further studies are required to better understand the physiopathological mechanisms of T2DM in these patients.
Journal ArticleDOI
"A LEAP 2 conclusions? Targeting the ghrelin system to treat obesity and diabetes".
TL;DR: It would not be a “leap to” conclusions to suggest that agents which target the ghrelin system – including those that lower acyl-ghrelin levels, raise LEAP2 levels, block GHSR activity, and/or raise desacyl-gh Relin signaling – could represent efficacious novel treatments for obesity and diabetes.
References
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Journal ArticleDOI
Ghrelin is a growth-hormone-releasing acylated peptide from stomach.
TL;DR: The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelIn, a peptide specifically releases GH both in vivo and in vitro.
Journal ArticleDOI
The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis
Michael A. Cowley,Roy G. Smith,Sabrina Diano,Matthias H. Tschöp,Nina Pronchuk,Kevin L. Grove,Christian J. Strasburger,Martin Bidlingmaier,Michael Esterman,Mark L. Heiman,Luis M. Garcia-Segura,Eduardo A. Nillni,Pablo Mendez,Malcolm J. Low,Péter Sótonyi,Jeffrey M. Friedman,Hongyan Liu,Shirly Pinto,William F. Colmers,Roger D. Cone,Tamas L. Horvath +20 more
TL;DR: Using electrophysiological recordings, ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH), thus representing a novel regulatory circuit controlling energy homeostasis.
Journal ArticleDOI
The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans
Sharmilee Gnanapavan,Blerina Kola,Stephen A. Bustin,Damian G. Morris,Patrick McGee,Peter D. Fairclough,Satya Bhattacharya,Robert Carpenter,Ashley B. Grossman,Márta Korbonits +9 more
TL;DR: The data suggest that ghrelin might have widespread physiological effects via different, partly unidentified, subtypes of the GHS-R in endocrine and non-endocrine tissues.
Journal ArticleDOI
Prader-Willi syndrome
TL;DR: Prader-Willi syndrome is characterized by severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal insufficiency; characteristic facial features; early-childhood onset obesity and hyperphagia; developmental delay/mild intellectual disability; short stature; and a distinctive behavioral phenotype.
Journal ArticleDOI
Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues.
Xiao-Ming Guan,Hong Yu,Oksana C. Palyha,Karen K. McKee,Scott D. Feighner,Dalip J. S. Sirinathsinghji,Roy G. Smith,Lex H.T. Van der Ploeg,Andrew D. Howard +8 more
TL;DR: The demonstration of hypothalamic and pituitary localization of the GHS-R is consistent with its role in regulating growth hormone release and the expression of the receptor in other central and peripheral regions may implicate its involvement in additional as yet undefined physiological functions.
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