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Melanocortin system

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https://www.readbyqxmd.com/read/28051332/activation-of-the-central-melanocortin-system-chronically-reduces-body-mass-without-the-necessity-of-long-term-caloric-restriction
#1
I Côté, Y Sakarya, N Kirichenko, D Morgan, C S Carter, N Tümer, P J Scarpace
Melanotan II (MTII) is a potent appetite suppressor that rapidly reduces body mass. Given the rapid loss of anorexic response upon chronic MTII treatment, most investigations have focused on the initial physiological adaptations. However, other evidence supports MTII as a long-term modulator of energy balance that remains to be established. Therefore, we examined the chronic effects of MTII on energy homeostasis. MTII (high or low dose) or artificial cerebrospinal fluid (aCSF) was infused into the lateral ventricle of the brain of 6-month-old F344BN rats (6-7/group) over 40 days...
October 19, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28048872/we-fg-bra-10-radiodosimetry-of-a-novel-alpha-particle-therapy-targeted-to-uveal-melanoma-absorbed-dose-to-organs-in-mice
#2
Christopher J Tichacek, Narges K Tafreshi, Mikalai M Budzevich, Epifanio Ruiz, Thaddeus J Wadas, Mark L McLaughlin, Eduardo G Moros, David L Morse
PURPOSE: The melanocortin-1 receptor (MC1R) is expressed in 94% of uveal melanomas and is described as an ideal target for this untreatable disease. MC1RL is a high affinity MC1R specific peptidomimetic ligand that can serve as a scaffold for therapeutic conjugates such as alpha particle emitting isotopes. The purpose of this study was to assess normal tissue distribution and risk as a result of using the DOTA chelator conjugated to MC1RL to deliver (225) Ac: MC1RL-DOTA-(225) Ac. METHODS: 17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-(225) Ac radiopharmaceutical with an average initial administered activity of 2...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045525/a-macrocyclic-agouti-related-protein-nle-4-dphe-7-%C3%AE-melanocyte-stimulating-hormone-chimeric-scaffold-produces-sub-nanomolar-melanocortin-receptor-ligands
#3
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 3, 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
#4
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
#5
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/28019657/the-melanoma-linked-redhead-mc1r-influences-dopaminergic-neuron-survival
#6
Xiqun Chen, Hongxiang Chen, Waijiao Cai, Michael Maguire, Bailiu Ya, Fuxing Zuo, Robert Logan, Hui Li, Katey Robinson, Charles R Vanderburg, Yang Yu, Yinsheng Wang, David E Fisher, Michael A Schwarzschild
OBJECTIVE: Individuals with Parkinson's disease are more likely to develop melanoma, and melanoma patients are reciprocally at higher risk of developing Parkinson's disease. Melanoma is strongly tied to red hair/fair skin, a phenotype of loss-of-function polymorphisms in the MC1R (melanocortin 1 receptor) gene. Loss-of-function variants of MC1R have also been linked to increased risk of Parkinson's disease. The present study is to investigate the role of MC1R in dopaminergic neurons in vivo...
December 26, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/28013339/genetics-of-obesity-can-an-old-dog-teach-us-new-tricks
#7
REVIEW
Giles S H Yeo
At one level, obesity is clearly a problem of simple physics, a result of eating too much and not expending enough energy. The more complex question, however, is why do some people eat more than others? Studies of human and mouse genetics over the past two decades have uncovered a number of pathways within the brain that play a key role in the control of food intake. A prime example is the leptin-melanocortin pathway, which we now know greatly contributes to mammalian appetitive behaviour. However, genetic disruption of this pathway remains rare and does not represent the major burden of the disease that is carried by those of us with 'common obesity'...
December 24, 2016: Diabetologia
https://www.readbyqxmd.com/read/28009464/effect-of-melanotan-ii-on-brain-fos-immunoreactivity-and-oxytocin-neuronal-activity-and-secretion-in-rats
#8
Luis Paiva, Nancy Sabatier, Gareth Leng, Mike Ludwig
Melanocortins stimulate the central oxytocin systems which are involved in regulating social behaviours. Alterations in central oxytocin have been linked to neurological disorders such as autism, and melanocortins have been proposed for therapeutic treatment. Here, we investigated how systemic administration of melanotan-II (MT-II), a melanocortin agonist, affects oxytocin neuronal activity and secretion in rats. Our results show that intravenous (i.v.), but not intranasal, administration of MT-II markedly induced Fos expression in magnocellular neurones of the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, and this response was attenuated by prior intracerebroventricular (i...
December 23, 2016: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/27931246/increased-alternate-splicing-of-htr2c-in-a-mouse-model-for-prader-willi-syndrome-leads-disruption-of-5ht2c-receptor-mediated-appetite
#9
Alastair S Garfield, Jennifer R Davies, Luke K Burke, Hannah V Furby, Lawrence S Wilkinson, Lora K Heisler, Anthony R Isles
Alternate splicing of serotonin (5-hydroxytryptamine; 5-HT) 2C receptor (5-HT2CR) pre-RNA is negatively regulated by the small nucleolar RNA, Snord115, loss of which is observed in nearly all individuals with Prader-Willi Syndrome (PWS), a multigenic disorder characterised by hyperphagia and obesity. Given the role of the 5-HT2CR in the regulation of ingestive behaviour we investigated the pathophysiological implications of Snord115 deficiency on 5-HT2CR regulated appetite in a genotypically relevant PWS mouse model (PWS-IC)...
December 8, 2016: Molecular Brain
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/27911598/type-3-deiodinase-role-on-central-thyroid-hormone-action-affects-the-leptin-melanocortin-system-and-circadian-activity
#11
Zhaofei Wu, M Elena Martinez, Donald L St Germain, Arturo Hernandez
The role of thyroid hormones (TH) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice due to defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3(-/-) brain is opposite that of the serum, exhibiting enhanced levels of TH action. Since the brain, specially the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3(-/-) mice and determine whether it is associated with hypothalamic abnormalities...
December 2, 2016: Endocrinology
https://www.readbyqxmd.com/read/27894065/evaluation-of-csf-and-plasma-biomarkers-of-brain-melanocortin-activity-in-response-to-caloric-restriction-in-humans
#12
Gabrielle Page-Wilson, Kim T Nguyen, Deniz Atalayer, Kana Meece, Heather A Bainbridge, Judith Korner, Rebecca J Gordon, Sunil K Panigrahi, Anne White, Richard Smiley, Sharon L Wardlaw
The melanocortin neuronal system, which consists of hypothalamic proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, is a leptin target that regulates energy balance and metabolism, but studies in humans are limited by a lack of reliable biomarkers to assess brain melanocortin activity. The objective of this study was to measure the POMC prohormone and its processed peptide, β-endorphin (β-EP), in cerebrospinal fluid (CSF) and AgRP in CSF and plasma after calorie restriction to validate their utility as biomarkers of brain melanocortin activity...
January 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
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
#13
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/27851802/str-profiling-for-discrimination-between-wild-and-domestic-swine-specimens-and-between-main-breeds-of-domestic-pigs-reared-in-belarus
#14
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/27829153/stimulation-of-the-hippocampal-pomc-mc4r-circuit-alleviates-synaptic-plasticity-impairment-in-an-alzheimer-s-disease-model
#15
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
#16
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
https://www.readbyqxmd.com/read/27791019/central-role-for-melanocortin-4-receptors-in-offspring-hypertension-arising-from-maternal-obesity
#17
Anne-Maj S Samuelsson, Amandine Mullier, Nuria Maicas, Nynke R Oosterhuis, Sung Eun Bae, Tatiana V Novoselova, Li F Chan, Joaquim M Pombo, Paul D Taylor, Jaap A Joles, Clive W Coen, Nina Balthasar, Lucilla Poston
Melanocortin-4 receptor (Mc4r)-expressing neurons in the autonomic nervous system, particularly in the paraventricular nucleus of the hypothalamus (PVH), play an essential role in blood pressure (BP) control. Mc4r-deficient (Mc4rKO) mice are severely obese but lack obesity-related hypertension; they also show a reduced pressor response to salt loading. We have previously reported that lean juvenile offspring born to diet-induced obese rats (OffOb) exhibit sympathetic-mediated hypertension, and we proposed a role for postnatally raised leptin in its etiology...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27775197/survival-by-genotype-patterns-at-mc1r-are-not-black-and-white-at-the-white-sands-ecotone
#18
S Des Roches, R Sollmann, K Calhoun, A P Rothstein, E B Rosenblum
Measuring links among genotype, phenotype and survival in the wild has long been a focus of studies of adaptation. We conducted a 4-year capture-recapture study to measure survival by genotype and phenotype in the Southwestern Fence Lizard (Sceloporus cowlesi) at the White Sands ecotone (transition area between white sands and dark soil habitats). We report several unanticipated findings. First, in contrast with previous work showing that cryptic blanched coloration in S. cowlesi from the heart of the dunes is associated with mutations in the melanocortin-1 receptor gene (Mc1r), ecotonal S...
October 24, 2016: Molecular Ecology
https://www.readbyqxmd.com/read/27728914/the-role-of-the-melanocortin-system-in-metabolic-disease-new-developments-and-advances
#19
Jennifer W Hill, Latrice D Faulkner
No abstract text is available yet for this article.
October 11, 2016: Neuroendocrinology
https://www.readbyqxmd.com/read/27725374/rnai-mediated-knockdown-of-mouse-melanocortin-4-receptor-in-vitro-and-in-vivo-using-an-sirna-expression-construct-based-on-the-mir-187-precursor
#20
Minoru Kato, Yi-Ying Huang, Mina Matsuo, Yoko Takashina, Kazuyo Sasaki, Yasushi Horai, Aya Juni, Shin-Ichi Kamijo, Kaoru Saigo, Kumiko Ui-Tei, Hajime Tei
RNA interference (RNAi) is a powerful tool for the study of gene function in mammalian systems, including transgenic mice. Here, we report a gene knockdown system based on the human mir-187 precursor. We introduced small interfering RNA (siRNA) sequences against the mouse melanocortin-4 receptor (mMc4r) to alter the targeting of miR-187. The siRNA-expressing cassette was placed under the control of the cytomegalovirus (CMV) early enhancer/chicken β-actin promoter. In vitro, the construct efficiently knocked down the gene expression of a co-transfected mMc4r-expression vector in cultured mammalian cells...
September 30, 2016: Experimental Animals
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