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https://www.readbyqxmd.com/read/28213370/promiscuity-among-the-mraps
#1
Adrian J L Clark, Li F Chan
The melanocortin 2 receptor accessory protein (MRAP) was originally discovered to be an essential co-receptor for the ACTH receptor/melanocortin 2 receptor, and it physically interacts with this receptor and is required for receptor trafficking and ligand binding. A related molecule, MRAP2, is mainly expressed in the CNS and appears to have a role with the melanocortin 4 receptor. Consistent with this is the observation that a massively obese phenotype develops when the Mrap2 gene is deleted in mice. However, the characteristics of this phenotype differ from those of Mc4r deleted mice, and suggest that an additional role, possibly resulting from an interaction with other receptors is possible...
February 17, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28197776/effects-of-melanocortin-4-receptor-agonists-and-antagonists-on-expression-of-genes-related-to-reproduction-in-spotted-scat-scatophagus-argus
#2
Dong-Neng Jiang, Jian-Tao Li, Ya-Xiong Tao, Hua-Pu Chen, Si-Ping Deng, Chun-Hua Zhu, Guang-Li Li
Melanocortin-4 receptor (Mc4r) function related to reproduction in fish has not been extensively investigated. Here, we report on gene expression changes by real-time PCR following treatment with Mc4r agonists and antagonists in the spotted scat (Scatophagus argus). Using in vitro incubated hypothalamus, the Mc4r nonselective agonist NDP-MSH ([Nle(4), D-Phe(7)]-α-melanocyte stimulating hormone; 10(-6) M) and selective agonist THIQ (N-[(3R)-1, 2, 3, 4-Tetrahydroisoquinolinium-3-ylcarbonyl]- (1R)-1-(4-chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl) piperidin-1-yl]-2-oxoethylamine; 10(-7) M) significantly increased the expression of gnrh (Gonadotropin releasing hormone), while the Mc4r nonselective antagonist SHU9119 (Ac-Nle-[Asp-His-DPhe/DNal(2')-Arg-Trp-Lys]-NH2; 10(-6) M) and selective antagonist Ipsen 5i (compound 5i synthesized in Ipsen Research Laboratories; 10(-6) M) significantly inhibited gnrh expression after 3 h of incubation...
February 14, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28152402/molecular-cloning-tissue-distribution-and-pharmacological-characterization-of-melanocortin-4-receptor-in-grass-carp-ctenopharyngodon-idella
#3
L Li, Z Yang, Y-P Zhang, S He, X-F Liang, Y-X Tao
Melanocortin-4 receptor (MC4R) plays a pivotal role in the mediation of leptin action on food intake and energy expenditure in mammals. The MC4R has also been identified in several teleosts, and its importance in the regulation of fish energy homeostasis is emerging. We herein reported on the molecular cloning, tissue distribution, and pharmacological characterization of MC4R in grass carp (Ctenopharyngodon idella), an economically and ecologically important fish. We showed that grass carp MC4R (ciMC4R) consisted of a 981 bp open reading frame encoding a protein of 326 amino acids, highly homologous (>95%) to several teleost MC4Rs...
November 21, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28150230/melanocortin-receptor-4-gene-polymorphisms-in-glioblastoma-patients-treated-with-concomitant-radio-chemotherapy
#4
Francesco Pasqualetti, Paola Orlandi, Vittorio Simeon, Martina Cantarella, Daniela Giuliani, Teresa Di Desidero, Alessandra Gonnelli, Durim Delishaj, Giuseppe Lombardi, Andrea Sechi, Marc Sanson, Vittorina Zagonel, Fabiola Paiar, Romano Danesi, Salvatore Guarini, Guido Bocci
Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled...
February 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28148682/dietary-protein-modifies-the-effect-of-the-mc4r-genotype-on-2-year-changes-in-appetite-and-food-craving-the-pounds-lost-trial
#5
Tao Huang, Yan Zheng, Adela Hruby, Donald A Williamson, George A Bray, Yiru Shen, Frank M Sacks, Lu Qi
BACKGROUND: The melanocortin-4 receptor (MC4R) plays a pivotal role in the regulation of appetite and eating behavior. Variants in the MC4R gene have been related to appetite and obesity. OBJECTIVE: We aimed to examine whether weight-loss diets modified the effect of the "obesity-predisposing" MC4R genotype on appetite-related measures in a randomized controlled trial. METHODS: A total of 811 overweight and obese subjects [25 ≤ body mass index (BMI; kg/m(2)) ≤ 40] aged 30-70 y were included in the 2-y POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) trial...
February 1, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28133617/molecular-analysis-of-a-genetic-variants-panel-related-to-nutrients-and-metabolism-association-with-susceptibility-to-gestational-diabetes-and-cardiometabolic-risk-in-affected-women
#6
Marica Franzago, Federica Fraticelli, Antonio Nicolucci, Claudio Celentano, Marco Liberati, Liborio Stuppia, Ester Vitacolonna
Gestational diabetes mellitus (GDM) is the most frequent metabolic disorder in pregnancy. Women with a GDM history are at increased risk of developing diabetes and cardiovascular diseases. Studies have demonstrated a significant correlation between several genes involved in the metabolic pathway of insulin and environmental factors. The aim of this study was to investigate the relationship between clinical parameters in GDM and variants in genes involved with nutrients and metabolism. Several variants PPARG2 rs1801282 (C>G); PPARGC1A rs8192678 (C>T); TCF7L2 rs7903146 (C>T); LDLR rs2228671 (C>T); MTHFR rs1801133 (C>T); APOA5 rs662799 (T>C); GCKR rs1260326 (C>T); FTO rs9939609 (T>A); MC4R rs17782313 (T>C) were genotyped in 168 pregnant Caucasian women with or without GDM by High Resolution Melting (HRM) analysis...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28128928/a-direct-in-vivo-comparison-of-the-melanocortin-monovalent-agonist-ac-his-dphe-arg-trp-nh2-versus-the-bivalent-agonist-ac-his-dphe-arg-trp-pedg20-his-dphe-arg-trp-nh2-a-bivalent-advantage
#7
Cody J Lensing, Danielle N Adank, Stacey L Wilber, Katie T Freeman, Sathya M Schnell, Robert Charles Speth, Adam T Zarth, Carrie Haskell-Luevano
Bivalent ligands targeting putative melanocortin receptor dimers have been developed and characterized in vitro, however studies of their functional in vivo effects have been limited. The current report compares the effects of homobivalent ligand CJL-1-87, Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH2, to monovalent ligand CJL-1-14, Ac-His-DPhe-Arg-Trp-NH2 on energy homeostasis in mice after central intracerebroventricular (ICV) administration into the lateral ventricle of the brain. Bivalent ligand CJL-1-87 had noteworthy advantages as an anti-obesity probe over CJL-1-14 in a fasting-refeeding in vivo paradigm...
January 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28093215/melanocortin-4-receptor-constitutive-activity-inhibits-l-type-voltage-gated-calcium-channels-in-neurons
#8
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 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28090739/obesity-related-genetic-polymorphisms-and-adiposity-indices-in-a-young-italian-population
#9
Laura Bordoni, Francesca Marchegiani, Marco Piangerelli, Valerio Napolioni, Rosita Gabbianelli
Pediatric obesity develops when a complex biological predisposition collides with an obesogenic environment. To further elucidate the role of genetics in obesity onset, we performed a candidate-gene association study in a young and sportive Italian population by testing the association of functional polymorphisms in ACE (rs4646994), FTO (rs9939609), MC4R (rs17782313) and PPARG (rs1801282) genes with body mass index (BMI) and waist-to-height ratio (WHtR). We also tested the combinations of identified risk genotypes and epistatic interactions among them to determine the existence of cumulative effects in predicting the predisposition to gain weight...
February 2017: IUBMB Life
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
#10
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
#11
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/28035522/analysis-of-gene-candidate-snp-and-ancestral-origin-associated-to-obesity-and-postoperative-weight-loss-in-a-cohort-of-obese-patients-undergoing-rygb
#12
David Velázquez-Fernández, Gabriela Mercado-Celis, Jeny Flores-Morales, Diana Clavellina-Gaytán, Ramón Vidrio, Eduardo Vidrio, Maureen Mosti, Hugo Sánchez-Aguilar, Donaji Rodriguez, Pablo León, Miguel F Herrera
INTRODUCTION: Obesity is the result of a complex interaction between multiple genetic traits and psychological, behavioral, nutritional and environmental factors. OBJECTIVES: The aims of the study were (a) to comparatively evaluate the presence of 20 candidate gene single nucleotide polymorphisms (SNPs) in morbidly obese patients, (2) their association to comorbid conditions and (3) their impact on weight loss after a Roux-en-Y gastric bypass (RYGB). PATIENTS AND METHODS: Two hundred forty-nine patients were eligible for this study...
December 29, 2016: Obesity Surgery
https://www.readbyqxmd.com/read/28025578/bmi-loci-and-longitudinal-bmi-from-adolescence-to-young-adulthood-in-an-ethnically-diverse-cohort
#13
M Graff, K E North, A S Richardson, K L Young, A L Mazul, H M Highland, K L Mohlke, L A Lange, E M Lange, K M Harris, P Gordon-Larsen
OBJECTIVE: The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood. SUBJECTS: In ancestry stratified models of 5962 European American (EA), 2080 African American (AA), and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity SNPs with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood...
December 27, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28003536/deficient-melanocortin-4-receptor-causes-abnormal-reproductive-neuroendocrine-profile-in-female-mice
#14
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/27991864/gs%C3%AE-deficiency-in-the-dorsomedial-hypothalamus-underlies-obesity-associated-with-gs%C3%AE-mutations
#15
Min Chen, Yogendra B Shrestha, Brandon Podyma, Zhenzhong Cui, Benedetta Naglieri, Hui Sun, Thuy Ho, Eric A Wilson, Yong-Qi Li, Oksana Gavrilova, Lee S Weinstein
Gsα, encoded by Gnas, mediates hormone and neurotransmitter receptor-stimulated cAMP generation. Heterozygous Gsα-inactivating mutations lead to obesity in Albright hereditary osteodystrophy (AHO) patients, but only when the mutations occur on the maternal allele. This parent-of-origin effect is due to Gsα imprinting in the CNS, although the relevant CNS regions are unknown. We have now shown that mice with a Gnas gene deletion disrupting Gsα expression on the maternal allele, but not the paternal allele, in the dorsomedial nucleus of the hypothalamus (DMH) developed obesity and reduced energy expenditure without hyperphagia...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27936173/insights-into-basal-signaling-regulation-oligomerization-and-structural-organization-of-the-human-g-protein-coupled-receptor-83
#16
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/27926527/meqtl-analysis-of-childhood-obesity-links-epigenetics-with-a-risk-snp-rs17782313-near-mc4r-from-meta-analysis
#17
Yuping Tang, Bo Jin, Lingling Zhou, Weifeng Lu
Earlier GWAS has identified that rs17782313 near MC4R was associated with obesity. However, subsequent studies showed conflicting results, especially among childhood. Besides, the mechanisms underlying the association between rs17782313 and childhood obesity remain largely unexplored, and genetic and epigenetic may interact and together affect the development of childhood obesity. We conducted a comprehensive meta-analysis to assess the association between rs17782313 and childhood obesity. MeQTL and eQTL analysis was applied to explore the effect of rs17782313 on DNA methylation and MC4R expression...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27920511/relationships-between-fto-rs9939609-mc4r-rs17782313-and-ppar%C3%AE-rs1801282-polymorphisms-and-the-occurrence-of-selected-metabolic-and-hormonal-disorders-in-middle-aged-and-elderly-men-a-preliminary-study
#18
Iwona Rotter, Karolina Skonieczna-Żydecka, Danuta Kosik-Bogacka, Grażyna Adler, Aleksandra Rył, Maria Laszczyńska
PURPOSE: Metabolic disorders, including MetS, obesity, and lipid disorders, may be related to genetic factors. Metabolic disorders are associated with decreased TS levels in aging men. The aim of this study was to evaluate the relationship between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the presence of MetS and its components, the concurrent lipid disorders, as well as sex hormone concentrations. SUBJECTS AND METHODS: This study involved 272 men of Caucasian descent aged 50-75 years...
2016: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/27911598/type-3-deiodinase-role-on-central-thyroid-hormone-action-affects-the-leptin-melanocortin-system-and-circadian-activity
#19
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/27890744/gene-expression-of-pro-opiomelanocortin-and-melanocortin-receptors-is-regulated-in-the-hypothalamus-and-mesocorticolimbic-system-following-nicotine-administration
#20
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
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