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Melanocortin

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https://www.readbyqxmd.com/read/28930194/developmental-programming-of-obesity-and-liver-metabolism-by-maternal-perinatal-nutrition-involves-the-melanocortin-system
#1
Paul Cordero, Jiawei Li, Vi Nguyen, Joaquim Pombo, Nuria Maicas, Marco Novelli, Paul D Taylor, Anne-Maj Samuelsson, Manlio Vinciguerra, Jude A Oben
Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit obesity during adulthood. Here, we aim to determine the influence of the Mc4r gene on the liver of mice subjected to perinatal diet-induced obesity. Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO)...
September 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28924523/the-interplay-of-genetics-and-environmental-factors-in-the-development-of-obesity
#2
REVIEW
Abu Baker Sheikh, Adeel Nasrullah, Shujaul Haq, Aisha Akhtar, Haider Ghazanfar, Amara Nasir, Rao M Afzal, Marvi M Bukhari, Ahtsham Yousaf Chaudhary, Syed W Naqvi
Obesity is a major health issue in the developed nations, and it has been increasingly clear that both genetics and environment play an important role in determining if an individual will be obese or not. We reviewed the latest researches which were carried out to identify the obesity susceptible genes and to identify the metabolic pathways having a central role in energy balance. Obesity is a heritable disorder, and some of the many obesity susceptible genes are fat mass and obesity (FTO), leptin, and Melanocortin-4 receptor (MC4R)...
July 6, 2017: Curēus
https://www.readbyqxmd.com/read/28916831/the-melanocortin-signaling-camp-axis-accelerates-repair-and-reduces-mutagenesis-of-platinum-induced-dna-damage
#3
Stuart G Jarrett, Katharine M Carter, Brent J Shelton, John A D'Orazio
Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915638/oleoylethanolamide-inhibits-%C3%AE-melanocyte-stimulating-hormone-stimulated-melanogenesis-via-erk-akt-and-creb-signaling-pathways-in-b16-melanoma-cells
#4
Juan Zhou, Tong Ren, Ying Li, Anran Cheng, Wanyi Xie, Lanxi Xu, Lu Peng, Jinbin Lin, Lianxiang Lian, Yong Diao, Xin Jin, Lichao Yang
The present study aimed to examine the potential inhibitory activity of oleoylethanolamide (OEA) on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis and the molecular mechanism(s) involved in the process in B16 mouse melanoma cells. Our data demonstrated that OEA markedly inhibited melanin synthesis and tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of melanogenesis-related proteins, such as melanocortin-1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and tyrosinase, was suppressed in a concentration-dependent manner by OEA...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904020/gtrap3-18-regulates-food-intake-and-body-weight-by-interacting-with-pro-opiomelanocortin
#5
Koji Aoyama, Wattanaporn Bhadhprasit, Masahiko Watabe, Fan Wang, Nobuko Matsumura, Toshio Nakaki
Pro-opiomelanocortin (POMC)-expressing neurons provide α-melanocyte-stimulating hormone (α-MSH), which stimulates melanocortin 4 receptor to induce hypophagia by AMPK inhibition in the hypothalamus. α-MSH is produced by POMC cleavage in secretory granules and released. However, it is not known yet whether any posttranscriptional regulatory mechanism of POMC signaling exists upstream of the secretory granules in neurons. Here we show that glutamate transporter-associated protein 3-18 (GTRAP3-18), an anchor protein that retains interacting proteins in the endoplasmic reticulum, is a critical regulator of food intake and body weight by interacting with POMC...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28902444/genomewide-association-studies-of-suicide-attempts-in-us-soldiers
#6
Murray B Stein, Erin B Ware, Colter Mitchell, Chia-Yen Chen, Susan Borja, Tianxi Cai, Catherine L Dempsey, Carol S Fullerton, Joel Gelernter, Steven G Heeringa, Sonia Jain, Ronald C Kessler, James A Naifeh, Matthew K Nock, Stephan Ripke, Xiaoying Sun, Jean C Beckham, Nathan A Kimbrel, Robert J Ursano, Jordan W Smoller
Suicide is a global public health problem with particular resonance for the US military. Genetic risk factors for suicidality are of interest as indicators of susceptibility and potential targets for intervention. We utilized population-based nonclinical cohorts of US military personnel (discovery: N = 473 cases and N = 9778 control subjects; replication: N = 135 cases and N = 6879 control subjects) and a clinical case-control sample of recent suicide attempters (N = 51 cases and N = 112 control subjects) to conduct GWAS of suicide attempts (SA)...
September 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28888694/analyzing-the-effects-of-co-expression-of-chick-gallus-gallus-melanocortin-receptors-with-either-chick-mrap1-or-mrap2-in-cho-cells-on-sensitivity-to-acth-1-24-or-acth-1-13-nh2-implications-for-the-avian-hpa-axis-and-avian-melanocortin-circuits-in-the-hypothalamus
#7
Alexa L Thomas, Fumihiko Maekawa, Takaharu Kawashima, Hirotaka Sakamoto, Tatsuya Sakamoto, Perry Davis, Robert M Dores
In order to better understand the roles that melanocortin receptors (cMCRs) and melanocortin-2 receptor accessory proteins (cMRAP1 and cMRAP2) play in the HPA axis and hypothalamus, adrenal gland and hypothalamus mRNA from 1day-old white leghorn chicks (Gallus gallus), were analyzed by real-time PCR. mRNA was also made for kidney, ovary, and liver. Mrap1 mRNA could be detected in adrenal tissue, but not in any of the other tissues, and mrap2 mRNA was also detected in the adrenal gland. Finally, all five melanocortin receptors mRNAs could be detected in the adrenal gland; mc2r and mc5r mRNAs were the most abundant...
September 6, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28878020/lipid-stress-inhibits-endocytosis-of-melanocortin-4-receptor-from-modified-clathrin-enriched-sites-and-impairs-receptor-desensitization
#8
Kimberly A Cooney, Brent M Molden, Nicholas S Kowalczyk, Susan Russell, Giulia Baldini
Melanocortin-4 receptor (MC4R) is a G protein coupled receptor expressed in the brain hypothalamus where it regulates energy homeostasis. MC4R agonists function to lower food intake and weight. In this respect, while obesity promotes hyperlipidemia and hypothalamic injury, MC4R agonists are nevertheless more effective to reduce food intake within hours of administration in overweight, rather than lean, mice. MC4R undergoes constitutive internalization and recycling to the plasma membrane, with agonist binding inducing receptor retention along the intracellular route and, under prolonged exposure, desensitization...
September 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28877366/melanocortin-receptor-subtypes-are-expressed-on-cells-in-the-oligodendroglial-lineage-and-signal-acth-protection
#9
Joyce A Benjamins, Liljana Nedelkoska, Robert P Lisak
ACTH, a melanocortin peptide used to treat multiple sclerosis (MS) relapses, acts by stimulating adrenal corticosteroid (CS) production via melanocortin receptor 2 (MC2R), but it may also exert a therapeutic effect independent of CS by stimulating other melanocortin receptors (MCR) distributed in many tissues, including the brain. We reported that oligodendroglia (OL) and oligodendroglial precursor cells (OPC) express MC4R, and that ACTH 1-39 protects OL and OPC in vitro from cell death induced by mechanisms likely involved in white matter damage in MS...
September 6, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28869973/palmitoylation-dependent-activation-of-mc1r-prevents-melanomagenesis
#10
Shuyang Chen, Bo Zhu, Chengqian Yin, Wei Liu, Changpeng Han, Baoen Chen, Tongzheng Liu, Xin Li, Xiang Chen, Chunying Li, Limin Hu, Jun Zhou, Zhi-Xiang Xu, Xiumei Gao, Xu Wu, Colin R Goding, Rutao Cui
The melanocortin-1 receptor (MC1R), a G-protein-coupled receptor, has a crucial role in human and mouse pigmentation. Activation of MC1R in melanocytes by α-melanocyte-stimulating hormone (α-MSH) stimulates cAMP signalling and melanin production and enhances DNA repair after ultraviolet irradiation. Individuals carrying MC1R variants, especially those associated with red hair colour, fair skin and poor tanning ability (denoted as RHC variants), are associated with higher risk of melanoma. However, how MC1R activity is modulated by ultraviolet irradiation, why individuals with red hair are more prone to developing melanoma, and whether the activity of RHC variants might be restored for therapeutic benefit are unknown...
September 6, 2017: Nature
https://www.readbyqxmd.com/read/28861897/beyond-mean-allelic-effects-a-locus-at-the-major-color-gene-mc1r-associates-also-with-differing-levels-of-phenotypic-and-genetic-co-variance-for-coloration-in-barn-owls
#11
Luis M San-Jose, Valérie Ducret, Anne-Lyse Ducrest, Céline Simon, Alexandre Roulin
The mean phenotypic effects of a discovered variant help to predict major aspects of the evolution and inheritance of a phenotype. However, differences in the phenotypic variance associated to distinct genotypes are often overlooked despite being suggestive of processes that largely influence phenotypic evolution, such as interactions between the genotypes with the environment or the genetic background. We present empirical evidence for a mutation at the melanocortin-1-receptor gene, a major vertebrate coloration gene, affecting phenotypic variance in the barn owl, Tyto alba...
September 1, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28860709/%C3%AE-melanocyte-stimulating-hormone-modulates-the-central-acyl-ghrelin-induced-stimulation-of-feeding-gastrointestinal-motility-and-colonic-secretion
#12
Hsien-Hao Huang, Liang-Yu Chen, Ming-Luen Doong, Shi-Chuan Chang, Chih-Yen Chen
BACKGROUND: Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect. OBJECTIVE: This study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28852042/the-mc4r-genotype-is-associated-with-postpartum-weight-reduction-and-glycemic-changes-among-women-with-prior-gestational-diabetes-longitudinal-analysis
#13
Aline Martins de Carvalho, Ping Shao, Huikun Liu, Han-Ling Cheng, Yan Zheng, Junhong Leng, Weiqin Li, Tao Huang, Tiange Wang, Leishen Wang, Shuang Zhang, Gang Hu, Lu Qi
The genetic variants near the Melanocortin-4 receptor gene (MC4R), a key protein regulating energy balance and adiposity, have been related to obesity and glucose metabolism. We aimed to assess whether the MC4R genotype affected longitudinal changes in body weight and glucose metabolism biomarkers among women with prior gestational diabetes mellitus (GDM). The MC4R genotype, postpartum weight reduction, and glycemic changes between after delivery and pregnancy were assessed in a cohort of 1208 Chinese women who had experienced GDM...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851815/epac-rap1-axis-mediated-switch-in-the-response-of-primary-and-metastatic-melanoma-to-cyclic-amp
#14
Carlos I Rodriguez, Edgardo Castro-Perez, Kirthana Prabhakar, Laura Block, B Jack Longley, Jaclyn A Wisinski, Michelle E Kimple, Vijayasaradhi Setaluri
Cyclic AMP (cAMP) is an important second messenger that regulates a wide range of physiological processes. In mammalian cutaneous melanocytes, cAMP-mediated signaling pathways activated by G-protein coupled receptors (GPCRs), like melanocortin 1 receptor (MC1R), play critical roles in melanocyte homeostasis including cell survival, proliferation and pigment synthesis. Impaired cAMP signaling is associated with increased risk of cutaneous melanoma. Whereas mutations in mitogen activated protein kinase (MAPK) pathway components are the most frequent oncogenic drivers of melanoma, the role of cAMP in melanoma is not well understood...
August 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28851749/the-thermogenic-effect-of-nesfatin-1-requires-recruitment-of-the-melanocortin-system
#15
Riccardo Dore, Luka Levata, Sogol Gachkar, Olaf Jöhren, Jens Mittag, Hendrik Lehnert, Carla Schulz
Nesfatin-1 is a bioactive polypeptide expressed both in the brain and peripheral tissues and involved in the control of energy balance by reducing food intake. Central administration of nesfatin-1 significantly increases energy expenditure, as demonstrated by a higher dry heat loss; yet, the mechanisms underlying the thermogenic effect of central nesfatin-1 remain unknown. Therefore, in this study, we sought to investigate whether the increase in energy expenditure induced by nesfatin-1 is mediated by the central melanocortin pathway, which was previously reported to mediate central nesfatin-1´s effects on feeding and numerous other physiological functions...
August 29, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28837761/diversification-and-convergence-of-aposematic-phenotypes-truncated-receptors-and-cellular-arrangements-mediate-rapid-evolution-of-coloration-in-harlequin-poison-frogs
#16
A Posso-Terranova, J A Andres
Aposematic signals represent one of the classical systems to study evolution and, as such, they have received considerable empirical and theoretical investigation. Despite the extensive literature on aposematic coloration, much uncertainty remains about genetic changes responsible for the repeated evolution of similar signals in multiple lineages. Here, we study the diversification and convergence of coloration among lineages of aposematic harlequin poison frogs (O. histrionica complex). Our results suggest that different background phenotypes, showing different color and/or luminance contrast, have evolved independently at least twice in this group...
August 24, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28829041/loss-of-the-melanocortin-4-receptor-in-mice-causes-dilated-cardiomyopathy
#17
Michael J Litt, G Donald Okoye, Daniel Lark, Isin Cakir, Christy Moore, Mary C Barber, James Atkinson, Josh Fessel, Javid Moslehi, Roger D Cone
Haploinsufficiency of the melanocortin-4 receptor, the most common monogenetic obesity syndrome in humans, is associated with a reduction in autonomic tone, bradycardia, and incidence of obesity-associated hypertension. Thus, it has been assumed that melanocortin obesity syndrome may be protective with respect to obesity-associated cardiovascular disease. We show here that absence of the melanocortin-4 receptor (MC4R) in mice causes dilated cardiomyopathy, characterized by reduced contractility and increased left ventricular diameter...
August 22, 2017: ELife
https://www.readbyqxmd.com/read/28828082/impact-of-the-polymorphism-near-mc4r-rs17782313-on-obesity-and-metabolic-related-traits-in-women-participating-in-an-aerobic-training-program
#18
Agata Leońska-Duniec, Zbigniew Jastrzębski, Aleksandra Zarębska, Wojciech Smółka, Paweł Cięszczyk
The C/T polymorphism (rs17782313) mapped 188 kb downstream of the melanocortin-4 receptor gene (MC4R) shows a strong relationship with an increased body mass index (BMI) and the risk of type 2 diabetes. However, the information on polymorphism's potential modifying effect on obesity- and metabolic-related traits achieved through training is still unknown. Therefore, we decided to check if selected body measurements observed in physically active participants would be modulated by the genotype. The genotype distribution was examined in a group of 201 Polish women measured for chosen traits before and after the completion of a 12 week moderate-intensive aerobic training program...
September 2017: Journal of Human Kinetics
https://www.readbyqxmd.com/read/28813605/structure-activity-relationship-studies-on-a-macrocyclic-agouti-related-protein-agrp-scaffold-reveal-agouti-signaling-protein-asp-residue-substitutions-maintain-melanocortin-4-receptor-antagonist-potency-and-result-in-inverse-agonist-pharmacology-at-the-melanocortin
#19
Mark D Ericson, Katie T Freeman, Sathya M Schnell, Katlyn A Fleming, Carrie Haskell-Luevano
The melanocortin system consists of five reported receptors, agonists from the proopiomelanocortin gene transcript, and two antagonists, agouti-signaling protein (ASP) and agouti-related protein (AGRP). For both ASP and AGRP, the hypothesized Arg-Phe-Phe pharmacophores are on exposed β-hairpin loops. In this study, the Asn and Ala positions of a reported AGRP macrocyclic scaffold (c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro]) were explored with 14-compound and 8-compound libraries, respectively, to generate more potent, selective melanocortin receptor antagonists...
August 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28812266/oxytocin-and-social-relationships-from-attachment-to-bond-disruption
#20
Oliver J Bosch, Larry J Young
Social relationships throughout life are vital for well-being and physical and mental health. A significant amount of research in animal models as well as in humans suggests that oxytocin (OT) plays an important role in the development of the capacity to form social bonds, the mediation of the positive aspects of early-life nurturing on adult bonding capacity, and the maintenance of social bonding. Here, we focus on the extensive research on a socially monogamous rodent model organism, the prairie vole (Microtus ochrogaster)...
August 16, 2017: Current Topics in Behavioral Neurosciences
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