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Melanocortin 4 receptor

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https://www.readbyqxmd.com/read/28103316/alpha-melanocyte-stimulating-hormone-protects-against-cytokine-induced-barrier-damage-in-caco-2-intestinal-epithelial-monolayers
#1
Judit Váradi, András Harazin, Ferenc Fenyvesi, Katalin Réti-Nagy, Péter Gogolák, György Vámosi, Ildikó Bácskay, Pálma Fehér, Zoltán Ujhelyi, Gábor Vasvári, Eszter Róka, David Haines, Mária A Deli, Miklós Vecsernyés
Alpha-melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and permeability for marker molecules...
2017: PloS One
https://www.readbyqxmd.com/read/28093215/melanocortin-4-receptor-constitutive-activity-inhibits-l-type-voltage-gated-calcium-channels-in-neurons
#2
F Agosti, S Cordisco Gonzalez, V Martinez Damonte, M J Tolosa, N Di Siervi, H B Schioth, C Davio, M Perello, J Raingo
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (CaV2...
January 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28081251/physical-activity-and-sedentary-behaviors-modify-the-association-between-melanocortin-4-receptor-gene-variant-and-obesity-in-chinese-children-and-adolescents
#3
Jie-Yun Song, Qi-Ying Song, Shuo Wang, Jun Ma, Hai-Jun Wang
Effects of MC4R variants in previous Chinese population studies were inconsistent. Gene-environment interactions might influence the effect of MC4R variants on obesity, which was still unclear. We performed the study to clarify the association of variants near MC4R gene with obesity-related phenotypes and gene-environment interactions in Chinese children and adolescents. Two common variants (rs12970134 and rs17782313) near MC4R were genotyped in 2179 children and adolescents aged 7-18 years in Beijing of China...
2017: PloS One
https://www.readbyqxmd.com/read/28045525/a-macrocyclic-agouti-related-protein-nle-4-dphe-7-%C3%AE-melanocyte-stimulating-hormone-chimeric-scaffold-produces-subnanomolar-melanocortin-receptor-ligands
#4
Mark D Ericson, Katie T Freeman, Sathya M Schnell, Carrie Haskell-Luevano
The melanocortin system consists of five receptor subtypes, endogenous agonists, and naturally occurring antagonists. These receptors and ligands have been implicated in numerous biological pathways including processes linked to obesity and food intake. Herein, a truncation structure-activity relationship study of chimeric agouti-related protein (AGRP)/[Nle4,DPhe7]α-melanocyte stimulating hormone (NDP-MSH) ligands is reported. The tetrapeptide His-DPhe-Arg-Trp or tripeptide DPhe-Arg-Trp replaced the Arg-Phe-Phe sequence in the AGRP active loop derivative c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was the native Asn of AGRP or a diaminopropionic (Dap) acid residue previously shown to increase antagonist potency at the mMC4R...
January 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28030540/severe-atherosclerosis-and-hypercholesterolemia-in-mice-lacking-both-the-melanocortin-type-4-receptor-and-low-density-lipoprotein-receptor
#5
Vera Lede, Christin Franke, Andrej Meusel, Daniel Teupser, Albert Ricken, Joachim Thiery, Jürgen Schiller, Daniel Huster, Torsten Schöneberg, Angela Schulz
Dysfunction of the melanocortin system can result in severe obesity accompanied with dyslipidemia and symptoms of the metabolic syndrome but the effect on vascular atherogenesis is not known. To study the impact of obesity and dyslipidemia on the cardiovascular system, we generated mice double-deficient for the melanocortin type 4 receptor (Mc4rmut mice) and the LDL receptor (Ldlr-/- mice). Mc4rmut mice develop obesity due to hyperphagia. Double-mutant mice (Mc4rmut;Ldlr-/-) exhibited massive increases in body weight, plasma cholesterol and triacylglycerol levels and developed atherosclerosis...
2016: PloS One
https://www.readbyqxmd.com/read/28028605/neuropeptide-systems-and-new-treatments-for-nicotine-addiction
#6
REVIEW
Adriaan W Bruijnzeel
RATIONALE: The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. OBJECTIVES: The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking...
December 28, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/28003536/deficient-melanocortin-4-receptor-causes-abnormal-reproductive-neuroendocrine-profile-in-female-mice
#7
Xiaolin Chen, Lili Huang, Hwee Y Tan, Hongzhuo Li, Ying Wan, Michael Cowley, Johannes D Veldhuis, Chen Chen
Deletion of the melanocortin-4-receptor (Mc4r) gene in mice causes hyperphagia, followed by hyperinsulinemia, obesity and progressive infertility. Evidence shows that the number of developed corpora lutea is reduced in obese MC4R-knockout (MC4R KO) female mice, but the mechanism is unclear. The effect of hyperphagia and obesity by MC4R KO on pulsatile luteinizing hormone (LH) secretion and ovulation remains unknown. In MC4R KO mice and wild-type littermates (WT LM) during the diestrus period throughout different ages, we examined and monitored their metabolic status, pulsatile LH profiles, follicular morphology and the number of corpora lutea...
March 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27977473/usefulness-of-ambulatory-blood-pressure-monitoring-to-assess-the-melanocortin-receptor-agonist-bremelanotide
#8
William B White, Martin G Myers, Robert Jordan, Johna Lucas
BACKGROUND: Melanocortin receptor agonists that bind to the melanocortin receptor 4 may cause increases in blood pressure (BP). Bremelanotide is an on-demand, subcutaneous melanocortin-receptor agonist that binds to the melanocortin receptor 4 and is being developed for the treatment of female sexual dysfunction. METHODS: We studied the effects of bremelanotide administration on ambulatory BP and heart rate (HR), in a randomized, double-blind, placebo-controlled, and parallel-arm trial of three doses of bremelanotide (0...
December 12, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27936173/insights-into-basal-signaling-regulation-oligomerization-and-structural-organization-of-the-human-g-protein-coupled-receptor-83
#9
Anne Müller, Julia Catherine Berkmann, Patrick Scheerer, Heike Biebermann, Gunnar Kleinau
The murine G-protein coupled receptor 83 (mGPR83) is expressed in the hypothalamus and was previously suggested to be involved in the regulation of metabolism. The neuropeptide PEN has been recently identified as a potent GPR83 ligand. Moreover, GPR83 constitutes functionally relevant hetero-oligomers with other G-protein coupled receptors (GPCR) such as the ghrelin receptor (GHSR) or GPR171. Previous deletion studies also revealed that the long N-terminal extracellular receptor domain (eNDo) of mGPR83 may act as an intra-molecular ligand, which participates in the regulation of basal signaling activity, which is a key feature of GPCR function...
2016: PloS One
https://www.readbyqxmd.com/read/27916623/multiple-beneficial-effects-of-melanocortin-mc4-receptor-agonists-in-experimental-neurodegenerative-disorders-therapeutic-perspectives
#10
REVIEW
Daniela Giuliani, Alessandra Ottani, Laura Neri, Davide Zaffe, Paolo Grieco, Jerzy Jochem, Gian Maria Cavallini, Anna Catania, Salvatore Guarini
Melanocortin peptides induce neuroprotection in acute and chronic experimental neurodegenerative conditions. Melanocortins likewise counteract systemic responses to brain injuries. Furthermore, they promote neurogenesis by activating critical signaling pathways. Melanocortin-induced long-lasting improvement in synaptic activity and neurological performance, including learning and memory, sensory-motor orientation and coordinated limb use, has been consistently observed in experimental models of acute and chronic neurodegeneration...
December 1, 2016: Progress in Neurobiology
https://www.readbyqxmd.com/read/27916541/the-orphan-g-protein-coupled-receptor-gpr139-is-activated-by-the-peptides-adrenocorticotropic-hormone-acth-%C3%AE-and-%C3%AE-melanocyte-stimulating-hormone-%C3%AE-msh-and-%C3%AE-msh-and-the-conserved-core-motif-hfrw
#11
Anne Cathrine Nøhr, Mohamed A Shehata, Alexander S Hauser, Vignir Isberg, Jacek Mokrosinski, Kirsten B Andersen, I Sadaf Farooqi, Daniel Sejer Pedersen, David E Gloriam, Hans Bräuner-Osborne
GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139...
January 2017: Neurochemistry International
https://www.readbyqxmd.com/read/27890744/gene-expression-of-pro-opiomelanocortin-and-melanocortin-receptors-is-regulated-in-the-hypothalamus-and-mesocorticolimbic-system-following-nicotine-administration
#12
Damla E Tapinc, Rabia Ilgin, Egemen Kaya, Oguz Gozen, Muzeyyen Ugur, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Pro-opiomelanocortin (POMC)-derived peptides and their receptors have been shown to play important roles in natural and drug-induced reward and reinforcement. Reward process may involve the regulation of POMC gene expression and the gene expression of POMC-derived peptide receptors. The present study investigated the alterations observed in the transcript levels of POMC, melanocortin 3 (MC3R), melanocortin 4 (MC4R) and mu-opioid receptors (MOR) in the hypothalamus and mesocorticolimbic system during nicotine exposure...
January 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27886210/physical-activity-energy-expenditure-and-defense-of-body-weight-in-melanocortin-4-receptor-deficient-male-rats
#13
Tariq I Almundarij, Mark E Smyers, Addison Spriggs, Lydia A Heemstra, Lisa Beltz, Eric Dyne, Caitlyn Ridenour, Colleen M Novak
Melanocortin 4 receptor (MC4R) variants contribute to human obesity, and rats lacking functional MC4R (Mc4r(K314X/K314X)) are obese. We investigated the hypothesis that low energy expenditure (EE) and physical activity contribute to this obese phenotype in male rats, and determined whether lack of functional MC4R conferred protection from weight loss during 50% calorie restriction. Though Mc4r(K314X/K314X) rats showed low brown adipose Ucp1 expression and were less physically active than rats heterozygous for the mutation (Mc4r(+/K314X)) or wild-type (Mc4r(+/+)) rats, we found no evidence of lowered EE in Mc4r(K314X/K314X) rats once body weight was taken into account using covariance...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27870313/hypothalamic-specific-proopiomelanocortin-deficiency-reduces-alcohol-drinking-in-male-and-female-mice
#14
Yan Zhou, Marcelo Rubinstein, Malcolm J Low, Mary Jeanne Kreek
Opioid receptor antagonist naltrexone reduces alcohol consumption and relapse in both humans and rodents. The present study investigated whether hypothalamic proopiomelanocortin (POMC) neurons (producing beta-endorphin and melanocortins) play a role in alcohol drinking behaviors. Both male and female mice with targeted deletion of two neuronal Pomc enhancers nPE1 and nPE2 (nPE-/-), resulting in hypothalamic-specific POMC deficiency, were studied in short-access (4-h/day) drinking-in-the-dark (DID, alcohol in one bottle), intermittent access (IA, 24-hour cycles of alcohol access every other day, alcohol vs...
November 21, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27869800/a-rapidly-acting-glutamatergic-arc%C3%A2-pvh-satiety-circuit-postsynaptically-regulated-by-%C3%AE-msh
#15
Henning Fenselau, John N Campbell, Anne M J Verstegen, Joseph C Madara, Jie Xu, Bhavik P Shah, Jon M Resch, Zongfang Yang, Yael Mandelblat-Cerf, Yoav Livneh, Bradford B Lowell
Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARC(AgRP) neurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARC(POMC)) neurons are viewed as the counterpoint to ARC(AgRP) neurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARC(AgRP) neurons, ARC(POMC) neurons are extremely slow in affecting hunger (many hours). Thus, a temporally analogous, rapid ARC satiety pathway does not exist or is presently unidentified...
January 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/27851802/str-profiling-for-discrimination-between-wild-and-domestic-swine-specimens-and-between-main-breeds-of-domestic-pigs-reared-in-belarus
#16
Krzysztof Rębała, Alina A Rabtsava, Svetlana A Kotova, Viachaslau N Kipen, Natalja V Zhurina, Alla I Gandzha, Iosif S Tsybovsky
A panel comprising 16 short tandem repeats (STRs) and a gender-specific amelogenin marker was worked out and tested for robustness in discrimination between wild and domestic swine subspecies encountered in Europe, between regional populations of wild boars and between main breeds of domestic pigs reared in Belarus. The STR dataset comprised 310 wild boars, inhabiting all administrative regions of Belarus, and 313 domestic pigs, representing three local and three cosmopolitan lines. Additionally, a total of 835 wild boars were genotyped for the presence of melanocortin 1 receptor (MC1R) alleles specific for domestic pigs...
2016: PloS One
https://www.readbyqxmd.com/read/27849360/robust-reductions-of-excess-weight-and-hyperphagia-by-beloranib-in-rat-models-of-genetic-and-hypothalamic-obesity
#17
Clinton T Elfers, Christian L Roth
Hypothalamic lesions or deficient melanocortin (MC) signaling via MC4 receptor (MC4r) mutations often lead to hyperphagia and severe treatment resistant obesity. We tested the methionine amino peptidase 2-inhibitor beloranib (ZGN-440) in two male rat models of obesity, one modeling hypothalamic obesity (HO) with combined medial hypothalamic lesions (CMHL), and the other modeling a monogenic form of obesity with MC4r mutations (MC4rKO). In CMHL rats (age 3 months), post-surgery excess weight gain was significantly inhibited (ZGN-440 0...
November 16, 2016: Endocrinology
https://www.readbyqxmd.com/read/27829468/fat-mass-obesity-associated-fto-rs9939609-and-melanocortin-4-receptor-mc4r-rs17782313-snp-are-positively-associated-with-obesity-and-blood-pressure-in-mexican-school-aged-children
#18
Pablo García-Solís, Marissa Reyes-Bastidas, Karla Flores, Olga P García, Jorge L Rosado, Lorena Méndez-Villa, Carlota Garcia-G, David García-Gutiérrez, Aarón Kuri-García, Hebert L Hernández-Montiel, Ofelia Soriano-Leon, Maria Elena Villagrán-Herrera, Juan C Solis-Sainz
Childhood overweight and obesity are worldwide public health problems and risk factors for chronic diseases. The presence of SNP in several genes has been associated with the presence of obesity. A total of 580 children (8-13 years old) from Queretaro, Mexico, participated in this cross-sectional study, which evaluated the associations of rs9939609 (fat mass obesity-associated (FTO)), rs17782313 (melanocortin 4 receptor (MC4R)) and rs6548238 (transmembrane protein 18 (TMEM18)) SNP with obesity and metabolic risk factors...
November 10, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27829153/stimulation-of-the-hippocampal-pomc-mc4r-circuit-alleviates-synaptic-plasticity-impairment-in-an-alzheimer-s-disease-model
#19
Yang Shen, Min Tian, Yuqiong Zheng, Fei Gong, Amy K Y Fu, Nancy Y Ip
Hippocampal synaptic plasticity is modulated by neuropeptides, the disruption of which might contribute to cognitive deficits observed in Alzheimer's disease (AD). Although pro-opiomelanocortin (POMC)-derived neuropeptides and melanocortin 4 receptor (MC4R) are implicated in hippocampus-dependent synaptic plasticity, how the POMC/MC4R system functions in the hippocampus and its role in synaptic dysfunction in AD are largely unknown. Here, we mapped a functional POMC circuit in the mouse hippocampus, wherein POMC neurons in the cornu ammonis 3 (CA3) activate MC4R in the CA1...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27797962/melanocortin-1-receptor-activation-is-neuroprotective-in-mouse-models-of-neuroinflammatory-disease
#20
Nadine Mykicki, Alexander M Herrmann, Nicholas Schwab, René Deenen, Tim Sparwasser, Andreas Limmer, Lydia Wachsmuth, Luisa Klotz, Karl Köhrer, Cornelius Faber, Heinz Wiendl, Thomas A Luger, Sven G Meuth, Karin Loser
In inflammation-associated progressive neuroinflammatory disorders, such as multiple sclerosis (MS), inflammatory infiltrates containing T helper 1 (TH1) and TH17 cells cause demyelination and neuronal degeneration. Regulatory T cells (Treg) control the activation and infiltration of autoreactive T cells into the central nervous system (CNS). In MS and experimental autoimmune encephalomyelitis (EAE) in mice, Treg function is impaired. We show that a recently approved drug, Nle(4)-d-Phe(7)-α-melanocyte-stimulating hormone (NDP-MSH), induced functional Treg, resulting in amelioration of EAE progression in mice...
October 26, 2016: Science Translational Medicine
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