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Melanocortin activity

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https://www.readbyqxmd.com/read/27911598/type-3-deiodinase-role-on-central-thyroid-hormone-action-affects-the-leptin-melanocortin-system-and-circadian-activity
#1
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
#2
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, comprised 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 lack of reliable biomarkers for brain melanocortin activity. The objective of this study was to measure the POMC prohormone and its processed peptide, ß-endorphin (ß-EP), in cerebrospinal fluid (CSF) and AgRP in CSF and plasma after calorie restriction to validate their utility as biomarkers of brain melanocortin activity...
November 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27886210/physical-activity-energy-expenditure-and-defense-of-body-weight-in-melanocortin-4-receptor-deficient-male-rats
#3
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/27869800/a-rapidly-acting-glutamatergic-arc%C3%A2-pvh-satiety-circuit-postsynaptically-regulated-by-%C3%AE-msh
#4
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...
November 21, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27853832/old-drugs-with-new-skills-fenoprofen-as-an-allosteric-enhancer-at-melanocortin-receptor-3
#5
Trinidad Montero-Melendez, Rachel A E Forfar, Jennifer M Cook, Jeffrey C Jerman, Debra L Taylor, Mauro Perretti
The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC3, MC4, and MC5 receptors...
November 16, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27849360/robust-reductions-of-excess-weight-and-hyperphagia-by-beloranib-in-rat-models-of-genetic-and-hypothalamic-obesity
#6
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/27829153/stimulation-of-the-hippocampal-pomc-mc4r-circuit-alleviates-synaptic-plasticity-impairment-in-an-alzheimer-s-disease-model
#7
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
#8
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/27754149/os-29-01-trans-generational-programming-of-obesity-related-hypertension-amplification-of-leptin-signalling-pathway
#9
Joon Kyungjoon Lim, Sandra Burke, Geoffrey Head
OBJECTIVE: Obesity during pregnancy is associated with a greater risk of developing hypertension in the offspring. Plasma leptin levels correlate strongly with blood pressure and renal sympathetic nerve activity (RSNA). The ventromedial hypothalamus (VMH) is a key centre of energy homeostasis, haemodynamic and sympathetic tone to renal vasculature. It is possible that exposure to over-nutrition during development change the activity of the neurons, amplifying sympathetic output leading to hypertension in the offspring...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27694057/melanoma-targeting-with-99m-tc-n-pnp3-labeled-%C3%AE-melanocyte-stimulating-hormone-peptide-analogs-effects-of-cyclization-on-the-radiopharmaceutical-properties
#10
Davide Carta, Nicola Salvarese, Nicolò Morellato, Feng Gao, Wiebke Sihver, Hans Jurgen Pietzsch, Barbara Biondi, Paolo Ruzza, Fiorenzo Refosco, Debora Carpanese, Antonio Rosato, Cristina Bolzati
The purpose of this study was to evaluate the effect of cyclization on the biological profile of a [(99m)Tc(N)(PNP3)]-labeled α-melanocyte stimulating hormone peptide analog. A lactam bridge-cyclized H-Cys-Ahx-βAla(3)-c[Lys(4)-Glu-His-D-Phe-Arg-Trp-Glu(10)]-Arg(11)-Pro-Val-NH2 (NAP-NS2) and the corresponding linear H-Cys-Ahx-βAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) peptide were synthetized, characterized by ESI-MS spectroscopy and their melanocortin-1 receptor (MC1R) binding affinity was determined in B16/F10 melanoma cells...
December 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27689001/adiponectin-potentiates-the-acute-effects-of-leptin-in-arcuate-pomc-neurons
#11
Jia Sun, Yong Gao, Ting Yao, Yiru Huang, Zhenyan He, Xingxing Kong, Kai-Jiang Yu, Rui-Tao Wang, Hongbo Guo, Jianqun Yan, Yongsheng Chang, Hong Chen, Philipp E Scherer, Tiemin Liu, Kevin W Williams
OBJECTIVE: Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation - including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27688998/defining-a-novel-leptin-melanocortin-kisspeptin-pathway-involved-in-the-metabolic-control-of-puberty
#12
Maria Manfredi-Lozano, Juan Roa, Francisco Ruiz-Pino, Richard Piet, David Garcia-Galiano, Rafael Pineda, Aurora Zamora, Silvia Leon, Miguel A Sanchez-Garrido, Antonio Romero-Ruiz, Carlos Dieguez, Maria Jesus Vazquez, Allan E Herbison, Leonor Pinilla, Manuel Tena-Sempere
OBJECTIVE: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic) health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27688995/%C3%AE-melanocyte-stimulating-hormone-promotes-muscle-glucose-uptake-via-melanocortin-5-receptors
#13
Pablo J Enriori, Weiyi Chen, Maria C Garcia-Rudaz, Bernadette E Grayson, Anne E Evans, Sarah M Comstock, Ursel Gebhardt, Hermann L Müller, Thomas Reinehr, Belinda A Henry, Russell D Brown, Clinton R Bruce, Stephanie E Simonds, Sara A Litwak, Sean L McGee, Serge Luquet, Sarah Martinez, Martin Jastroch, Matthias H Tschöp, Matthew J Watt, Iain J Clarke, Christian L Roth, Kevin L Grove, Michael A Cowley
OBJECTIVE: Central melanocortin pathways are well-established regulators of energy balance. However, scant data exist about the role of systemic melanocortin peptides. We set out to determine if peripheral α-melanocyte stimulating hormone (α-MSH) plays a role in glucose homeostasis and tested the hypothesis that the pituitary is able to sense a physiological increase in circulating glucose and responds by secreting α-MSH. METHODS: We established glucose-stimulated α-MSH secretion using humans, non-human primates, and mouse models...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27643079/os-29-01-trans-generational-programming-of-obesity-related-hypertension-amplification-of-leptin-signalling-pathway
#14
Joon Kyungjoon Lim, Sandra Burke, Geoffrey Head
OBJECTIVE: Obesity during pregnancy is associated with a greater risk of developing hypertension in the offspring. Plasma leptin levels correlate strongly with blood pressure and renal sympathetic nerve activity (RSNA). The ventromedial hypothalamus (VMH) is a key centre of energy homeostasis, haemodynamic and sympathetic tone to renal vasculature. It is possible that exposure to over-nutrition during development change the activity of the neurons, amplifying sympathetic output leading to hypertension in the offspring...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27633503/2-ethoxybenzamide-stimulates-melanin-synthesis-in-b16f1-melanoma-cells-via-the-creb-signaling-pathway
#15
Kazuomi Sato, Ryosuke Ando, Honoka Kobayashi, Takashi Nishio
Non-steroidal anti-inflammatory drugs are frequently used for the treatment of inflammation, pain, and fever. In this study, we found that 2-ethoxybenzamide (ETZ) significantly enhanced melanin synthesis in B16F1 melanoma cells, and also induced melanosome formation. Therefore, we investigated the mechanism by which ETZ up-regulated melanin synthesis. Western blot analysis demonstrated that ETZ increased melanogenic protein levels, except that for TRP-2. Moreover, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR analyses showed that ETZ enhanced the mRNA levels of melanogenic genes, including microphthalmia-associated transcription factor and melanocortin 1 receptor...
September 16, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27623943/tumour-biology-of-obesity-related-cancers-understanding-the-molecular-concept-for-better-diagnosis-and-treatment
#16
Seong Lin Teoh, Srijit Das
Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death...
September 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27612207/exchange-factors-directly-activated-by-camp-mediate-melanocortin-4-receptor-induced-gene-expression
#17
Evi Glas, Harald Mückter, Thomas Gudermann, Andreas Breit
Gs protein-coupled receptors regulate many vital body functions by activation of cAMP response elements (CRE) via cAMP-dependent kinase A (PKA)-mediated phosphorylation of the CRE binding protein (CREB). Melanocortin 4 receptors (MC4R) are prototypical Gs-coupled receptors that orchestrate the hypothalamic control of food-intake and metabolism. Remarkably, the significance of PKA for MC4R-induced CRE-dependent transcription in hypothalamic cells has not been rigorously interrogated yet. In two hypothalamic cell lines, we observed that blocking PKA activity had only weak or no effects on reporter gene expression...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27609221/epigenomic-and-metabolic-responses-of-hypothalamic-pomc-neurons-to-gestational-nicotine-exposure-in-adult-offspring
#18
Jose P Silva, Guerline Lambert, Derek van Booven, Claes Wahlestedt
BACKGROUND: Epidemiological and animal studies have reported that prenatal nicotine exposure (PNE) leads to obesity and type-2 diabetes in offspring. Central leptin-melanocortin signaling via hypothalamic arcuate proopiomelanocortin (POMC) neurons is crucial for the regulation of energy and glucose balance. Furthermore, hypothalamic POMC neurons were recently found to mediate the anorectic effects of nicotine through activation of acetylcholine receptors. Here, we hypothesized that PNE impairs leptin-melanocortinergic regulation of energy balance in first-generation offspring by altering expression of long non-coding RNAs (lncRNAs) putatively regulating development and/or function of hypothalamic POMC neurons...
2016: Genome Medicine
https://www.readbyqxmd.com/read/27582758/significance-of-the-melanocortin-1-and-endothelin-b-receptors-in-melanocyte-homeostasis-and-prevention-of-sun-induced-genotoxicity
#19
REVIEW
Viki B Swope, Zalfa A Abdel-Malek
The membrane bound melanocortin 1 receptor (MC1R), and the endothelin B receptor (ENDBR) are two G-protein coupled receptors that play important roles in constitutive regulation of melanocytes and their response to ultraviolet radiation (UVR), the main etiological factor for melanoma. The human MC1R is a Gs protein-coupled receptor, which is activated by its agonists α-melanocyte stimulating hormone (α-melanocortin; α-MSH) and adrenocorticotropic hormone (ACTH). The ENDBR is a Gq coupled-receptor, which is activated by Endothelin (ET)-3 during embryonic development, and ET-1 postnatally...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27576578/vagal-blocking-for-obesity-control-a-possible-mechanism-of-action
#20
Helene Johannessen, David Revesz, Yosuke Kodama, Nikki Cassie, Karolina Skibicka, Perry Barrett, Suzanne Dickson, Jens Holst, Jens Rehfeld, Geoffrey van der Plasse, Roger Adan, Bård Kulseng, Elinor Ben-Menachem, Chun-Mei Zhao, Duan Chen
BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device with leads placed around gastric vagal trunks through an abdominal incision and controlled by wireless device. Body weight, food intake, hunger/satiety, and metabolic parameters were monitored by a comprehensive laboratory animal monitoring system...
August 30, 2016: Obesity Surgery
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