Genomes and Genes
melanocortin 4 receptor
Gene Symbol: melanocortin 4 receptor
Description: melanocortin 4 receptor
Alias: melanocortin receptor 4, MC4-R
Publications256 found, 100 shown here
- A frameshift mutation in MC4R associated with dominantly inherited human obesityG S Yeo
Nat Genet 20:111-2. 1998
- Common variants near MC4R are associated with fat mass, weight and risk of obesityRuth J F Loos
MRC Epidemiology Unit, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
Nat Genet 40:768-75. 2008....
- Functional analyses of melanocortin-4 receptor mutations identified from patients with binge eating disorder and nonobese or obese subjectsYa Xiong Tao
Department of Physiology and Biophysics, The University of Iowa Carver College of Medicine, Iowa City 52242, USA
J Clin Endocrinol Metab 90:5632-8. 2005..Whether mutations in the melanocortin-4 receptor (MC4R) are the cause of binge eating disorder was controversial. In addition, the penetrance of mutations in the MC4R in causing obesity was debated...
- Clinical spectrum of obesity and mutations in the melanocortin 4 receptor geneI Sadaf Farooqi
University Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, United Kingdom
N Engl J Med 348:1085-95. 2003b>Melanocortin 4 receptor (MC4R) deficiency is the commonest monogenic form of obesity...
- Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brainK G Mountjoy
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201 3098
Mol Endocrinol 8:1298-308. 1994..The high degree of conservation, distinct pharmacology, and unique neuronal distribution of the MC4 receptor suggest specific and complex roles for the melanocortin peptides in neuroendocrine and autonomic control...
- Combined effects of FTO rs9939609 and MC4R rs17782313 on obesity and BMI in Chinese Han populationsWei Huang
Division of Endocrinology, Department of Puren Hospital, Wuhan University of Science and Technology, Wuhan, China
Endocrine 39:69-74. 2011..Their combined effects were significant in Chinese population. No association between FTO and MC4R and Chinese population with T2DM was found...
- Mutations in melanocortin-4 receptor and human obesityYa Xiong Tao
Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849, USA
Prog Mol Biol Transl Sci 88:173-204. 2009..Based on the defects, the mutants can be classified into five classes. Potential therapeutic implications from the analyses of the naturally occurring MC4R mutations, such as novel ligands and pharmacological chaperones, are highlighted...
- Investigation of a genome wide association signal for obesity: synthetic association and haplotype analyses at the melanocortin 4 receptor gene locusAndre Scherag
Institute of Medical Informatics, Biometry and Epidemiology, University of Duisburg Essen, Essen, Germany
PLoS ONE 5:e13967. 2010..two single nucleotide polymorphisms (SNP; rs12970134 and rs17782313) more than 150 kb downstream of the melanocortin 4 receptor gene (MC4R)...
- Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eatingCecile Lubrano-Berthelier
Diabetes Center and Department of Medicine, University of California San Francisco, San Francisco, California 94143 0573, USA
J Clin Endocrinol Metab 91:1811-8. 2006..There are conflicting reports regarding the prevalence, nature, and pathogenic effects of MC4R mutations in adults with severe late-onset obesity...
- Evaluation of genetic susceptibility loci for obesity in Chinese womenJiajun Shi
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Am J Epidemiol 172:244-54. 2010..Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations...
- Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populationsDavid Meyre
CNRS 8090 Institute of Biology, Pasteur Institute, 59000 Lille, France
Nat Genet 41:157-9. 2009..9 x 10(-7)), near MAF (encoding the transcription factor c-MAF, P = 3.8 x 10(-13)) and near PTER (phosphotriesterase-related gene, P = 2.1 x 10(-7))...
- Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP studyY Tabara
Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan
Int J Obes (Lond) 33:1243-8. 2009..Polymorphisms in the melanocortin 4 receptor (MC4R) gene were recently explored as another susceptible locus...
- Common polymorphism near the MC4R gene is associated with type 2 diabetes: data from a meta-analysis of 123,373 individualsB Xi
Department of Maternal and Child Health Care, School of Public Health, Shandong University, 44 Wenhuaxi Road, Jinan 250012, People s Republic of China
Diabetologia 55:2660-6. 2012Genome-wide association studies have shown that variants near the melanocortin 4 receptor gene (MC4R) (rs17782313 and rs12970134) are associated with risk of obesity in Europeans...
- Lower metabolic rate in individuals heterozygous for either a frameshift or a functional missense MC4R variantJonathan Krakoff
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, Phoenix, AZ, USA
Diabetes 57:3267-72. 2008Humans with functional variants in the melanocortin 4 receptor (MC4R) are obese, hyperphagic, and hyperinsulinemic but have been reported to have no difference in energy expenditure.
- The human intronless melanocortin 4-receptor gene is NMD insensitiveKatja S Brocke
Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 150, D 69120 Heidelberg, Germany
Hum Mol Genet 11:331-5. 2002..Thus, the naturally intronless MC4-R gene and probably many other intronless genes fail to be monitored by the NMD pathway...
- Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalizationHiroshi Shinyama
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Endocrinology 144:1301-14. 2003..Our data demonstrate that, through PKA-, GRK-, beta-arrestin-, and dynamin-dependent processes, MC4R undergoes internalization in response to agonist, thereby providing novel insights into the regulation of MC4R signaling...
- Molecular mechanism of the constitutive activation of the L250Q human melanocortin-4 receptor polymorphismBettina Proneth
Department of Medicinal Chemistry, University of Florida, PO Box 100485, Gainesville, FL 32610 0485, USA
Chem Biol Drug Des 67:215-29. 2006....
- A two-base deletion -439delGC in the melanocortin-4 receptor promoter associated with early-onset obesityKaisa Valli-Jaakola
Department of Medicine and Research Program in Molecular Medicine, University of Helsinki, Helsinki, Finland
Horm Res 66:61-9. 2006..We searched for mutations in MC4R promoter and Nhlh2 gene in 152 children with severe early-onset obesity. Lean subjects (n = 447) served as controls...
- Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesityNicola Santoro
Dipartimento di Pediatria F, Fede, Seconda Universita degli Studi di Napoli, Napoli, Italy
BMC Med Genet 10:25. 2009..To verify whether MC4R mutations are associated with this particular phenotype in the Italian pediatric population, we decided to screen the MC4R gene in a group of obese children selected on the basis of their phenotype...
- Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family StudyY C Chagnon
Physical Activity Sciences Laboratory, Laval University, Ste Foy, Quebec, Canada
Mol Med 3:663-73. 1997....
- High affinity agonistic metal ion binding sites within the melanocortin 4 receptor illustrate conformational change of transmembrane region 3Malin C Lagerström
Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden
J Biol Chem 278:51521-6. 2003We created a molecular model of the human melanocortin 4 receptor (MC4R) and introduced a series of His residues into the receptor protein to form metal ion binding sites...
- Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humansSupriya Srinivasan
Gladstone Institute of Cardiovascular Disease, UCSF, San Francisco, California 94143 0540, USA
J Clin Invest 114:1158-64. 2004..Our results also suggest that the tonic satiety signal provided by the constitutive activity of MC4R may be required for maintaining long-term energy homeostasis in humans...
- Obesity and eating behaviour in a three-generation Chilean family with carriers of the Thrl50Ile mutation in the melanocortin-4 receptor geneJ L Santos
Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Catolica de Chile
J Physiol Biochem 64:205-10. 2008It has been proposed that functional mutations in the melanocortin 4 receptor (MC4R) gene have an important impact in body mass index, being considered as a major susceptibility gene for obesity...
- Mutations in the melanocortin 4 receptor (MC4R) gene in obese patients in NorwayT Wangensteen
Department of Medical Genetics, Ulleval University Hospital, Oslo, Norway
Exp Clin Endocrinol Diabetes 117:266-73. 2009Mutations in the melanocortin 4 receptor ( MC4R) gene are the most frequent cause of monogenic forms of obesity, but the reported prevalences of mutations in obese individuals diverge, varying from 0.2 to 5.8%.
- Replication of association between a common variant near melanocortin-4 receptor gene and obesity-related traits in Asian SikhsLatonya F Been
Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Obesity (Silver Spring) 18:425-9. 2010..These observations demonstrate that the genetic variation in MC4R locus can have a moderate contribution in the regional fat deposition and development of central obesity in Asian Indians...
- Potent and selective agonism of the melanocortin receptor 4 with MK-0493 does not induce weight loss in obese human subjects: energy intake predicts lack of weight loss efficacyR Krishna
Merck and Co, Inc, Whitehouse Station, New Jersey, USA
Clin Pharmacol Ther 86:659-66. 2009MK-0493 is a novel, potent, and selective agonist of the melanocortin receptor 4 (MC4R), one of the best-validated genetic targets and considered one of the most promising for the development of antiobesity therapeutics...
- Melanocortin 4 receptor mutations in obese Czech children: studies of prevalence, phenotype development, weight reduction response, and functional analysisIrena Hainerova
Department of Pediatrics and Center for Research of Diabetes, Metabolism, and Nutrition, Third Faculty of Medicine, Charles University, 100 34 Prague 10, Czech Republic
J Clin Endocrinol Metab 92:3689-96. 2007Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common known cause of monogenic human obesity.
- Influence of common variants near INSIG2, in FTO, and near MC4R genes on overweight and the metabolic profile in adolescence: the TRAILS (TRacking Adolescents' Individual Lives Survey) StudyEryn T Liem
Department of Pediatrics Beatrix Children s Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Am J Clin Nutr 91:321-8. 2010..Overweight is a complex trait in which both environmental and genetic factors play a role...
- Genes and lifestyle factors in obesity: results from 12,462 subjects from MONICA/KORAC Holzapfel
Else Kroner Fresenius Center for Nutritional Medicine, Technische Universitat Munchen, Munich, Germany
Int J Obes (Lond) 34:1538-45. 2010..It was consecutively hypothesized that these associations might be evoked by a modulation of nutritional intake or energy expenditure...
- Obesity-linked variants of melanocortin-4 receptor are misfolded in the endoplasmic reticulum and can be rescued to the cell surface by a chemical chaperoneSusana Granell
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Slot 516, 4301 West Markham, Little Rock, AR 72205, USA
Mol Endocrinol 24:1805-21. 2010..These data offer a cell-based rationale that drugs that improve MC4R folding or decrease ER-associated degradation of the receptor may function to treat some forms of hereditary obesity...
- Melanocortin-4 receptor mutations in obesityFerruccio Santini
Department of Endocrinology and Kidney, University Hospital of Pisa, 56124 Pisa, Italy
Adv Clin Chem 48:95-109. 2009....
- A novel nonsense mutation in the melanocortin-4 receptor associated with obesity in a Spanish populationA Marti
Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain
Int J Obes Relat Metab Disord 27:385-8. 2003..reported dominant inheritance of obesity conferred by missense, nonsense and frameshift mutations in the melanocortin 4 receptor gene (MC4R). Hence, MC4R is involved in the most common monogenic form of human obesity described so far.
- Functional characterization of melanocortin-4 receptor mutations associated with childhood obesityYa Xiong Tao
Department of Physiology and Biophysics, 5 471 Bowen Science Building, The University of Iowa, Iowa City, Iowa 52242, USA
Endocrinology 144:4544-51. 2003..Our data, therefore, stress the importance of characterizing the properties of MC4R variants associated with early-onset severe obesity. We further propose a classification scheme for mutant MC4Rs based upon their properties...
- A homozygous null mutation delineates the role of the melanocortin-4 receptor in humansCecile Lubrano-Berthelier
Department of Medicine, University of California, San Francisco, California 94143 0573, USA
J Clin Endocrinol Metab 89:2028-32. 2004..In addition, complete MC4R deficiency is not a cause of relative hyperinsulinemia as recently observed in children with heterozygous MC4R mutations...
- Engineering the melanocortin-4 receptor to control constitutive and ligand-mediated G(S) signaling in vivoSupriya Srinivasan
Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, San Francisco, California, United States of America
PLoS ONE 2:e668. 2007..Our study also demonstrates the use of human genetic variation for protein engineering...
- Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humansA Hinney
Clinical Research Group, Department of Child and Adolescent Psychiatry, University of Marburg, FRG
J Clin Endocrinol Metab 84:1483-6. 1999..Whereas our data support the evidence for dominantly inherited obesity as revealed by the three obese probands with haplo-insufficiency, the functional significance of the missense mutations remains to be determined...
- Identification of domains directing specificity of coupling to G-proteins for the melanocortin MC3 and MC4 receptorsChung Sub Kim
Laboratory of Molecular Biology, Medical Research Center, Department of Pharmacology, College of Medicine, Brain Korea 21 Project for Medical Sciences, Yonsei University, Seoul 120 752, South Korea
J Biol Chem 277:31310-7. 2002..Overall, this study demonstrated that MC3R and MC4R have distinct signaling in either the cAMP- or the inositol phospholipid-mediated pathway with different conformational requirements...
- A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanismBenjamin G Challis
University Department of Medicine, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
Hum Mol Genet 11:1997-2004. 2002..These results suggest that the R236G mutation may confer an inherited susceptibility to obesity through the production of an aberrant fusion protein that has the capacity to interfere with central melanocortin signalling...
- Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohortPeter Jacobson
Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA
J Clin Endocrinol Metab 87:4442-6. 2002The prevalence of mutations within and in the flanking regions of the gene encoding the melanocortin 4 receptor was investigated in severely obese and normal-weight subjects from the Swedish Obese Subjects study, the Health, Risk Factors,..
- Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanismsGiles S H Yeo
Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 2XY, UK
Hum Mol Genet 12:561-74. 2003....
- beta-MSH: a functional ligand that regulated energy homeostasis via hypothalamic MC4-R?Joanne A Harrold
Department of Medicine, University of Liverpool, Daulby Street, L69 3GA Liverpool, UK
Peptides 24:397-405. 2003..We suggest that beta-MSH rather than alpha-MSH is the key ligand at the MC4-R populations that regulate feeding, and that inhibition of tonic release of beta-MSH is one mechanism contributing to hunger in under-feeding...
- Identification and characterization of melanocortin-4 receptor gene mutations in morbidly obese finnish children and adultsKaisa Valli-Jaakola
Department of Medicine and Research Program in Molecular Medicine, University of Helsinki, FIN 00290 Helsinki, Finland
J Clin Endocrinol Metab 89:940-5. 2004..Impaired function of the S127L receptor was due to reduced activation, not a defect of protein transport to the cell membrane...
- Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese populationRong Rong
Department of Medicine, Li Ka Shing Medical Faculty, The University of Hong Kong, Pokfulam, Hong Kong, China
Clin Endocrinol (Oxf) 65:198-205. 2006..We studied the frequency of MC4R mutations in an obese southern Chinese population and the functional consequences of the novel variants identified...
- Role of third intracellular loop of the melanocortin 4 receptor in the regulation of constitutive activityDo Hun Kim
Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 136 701, South Korea
Biochem Biophys Res Commun 365:439-45. 2008The melanocortin 4 receptor (MC4R) has been reported to display constitutive activity, which is probably relevant to the maintenance of a normal energy balance...
- Common genetic variation near MC4R is associated with eating behaviour patterns in European populationsF Stutzmann
1CNRS 8090 Institute of Biology, Pasteur Institute, Lille, France
Int J Obes (Lond) 33:373-8. 2009..The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation...
- Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesityE Miraglia del Giudice
Dipartimento de Pediatria, Seconda Universita di Napoli, Napoli, Italy
Int J Obes Relat Metab Disord 26:647-51. 2002..Melanocortin-4 receptor (MC4R) mutations have been reported as the most common single genetic cause of obesity in some populations and it has been suggested that they may be responsible for more than 4% of early-onset obesity...
- Binge eating as a major phenotype of melanocortin 4 receptor gene mutationsRuth Branson
Klinik Hirslanden, Zurich, Switzerland
N Engl J Med 348:1096-103. 2003..A few mutations in these genes, such as in the leptin receptor (LEPR) gene and melanocortin 4 receptor (MC4R) gene, have been identified as causes of monogenic obesity.
- Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesityAnke Hinney
Clinical Research Group, Department of Child and Adolescent Psychiatry, Philipps University of Marburg, D 35039 Marburg, Germany
J Clin Endocrinol Metab 88:4258-67. 2003..8% (P = 0.033; exact one-sided McNemar test). These results support the hypothesis that these MC4R mutations represent major gene effects for obesity...
- Modeling and docking of the three-dimensional structure of the human melanocortin 4 receptorXiaonan Yang
Laboratory of Bioinformatics, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
J Protein Chem 22:335-44. 2003A three-dimensional structure of the human melanocortin 4 receptor (hMC4R) is constructed in this study using a computer-aided molecular modeling approach. Human melanocortin 4 receptor is a G Protein-Coupled Receptor (GPCR)...
- Mutationally induced disulfide bond formation within the third extracellular loop causes melanocortin 4 receptor inactivation in patients with obesityPatrick Tarnow
Otto Heubner Centrum für Kinderheilkunde und Jugendmedizin, Pädiatrische Endokrinologie, Charite Campus Virchow Klinikum, Humboldt Universitat zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
J Biol Chem 278:48666-73. 2003By screening patients with severe early onset obesity for mutations within the melanocortin 4 receptor (MC4R) gene, we have identified a missense mutation (C271R) that occurs homozygous in two siblings with obesity...
- Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutationsJ Hebebrand
Department of Child and Adolescent Psychiatry of the Philipps University of Marburg, Germany
Mol Psychiatry 9:796-800. 2004..In particular, we found no evidence for an increased rate of binge-eating behavior in obese carriers of MC4R variants. Our findings do not support the strong association between BED and MC4R carrier status...
- Melanocortin 4 receptor gene variation is associated with severe obesity in Pima IndiansLijun Ma
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, 4212 N 16th St, Phoenix, AZ 85016, USA
Diabetes 53:2696-9. 2004Heterozygous coding mutations in the melanocortin 4 receptor gene (MC4R) are the most common genetic causes of severe human obesity identified to date...
- Large quantitative effect of melanocortin-4 receptor gene mutations on body mass indexA Dempfle
J Med Genet 41:795-800. 2004
- Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesityLesli H Larsen
Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 6, NSK 1 14, 2820 Gentofte, Denmark
J Clin Endocrinol Metab 90:219-24. 2005Mutations in the gene encoding the melanocortin 4 receptor (MC4R) are associated with the most common monogenic form of obesity. We examined 750 Danish men with juvenile-onset obesity (body mass index 33.3 +/- 2...
- Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity geneFanny Stutzmann
CNRS 8090 Institute of Biology, Pasteur Institute, Lille, France
Hum Mol Genet 16:1837-44. 2007..These results also emphasize the importance of the MC4R signalling tonus to prevent obesity, even in the context of our current obesogenic environment...
- Peptide and small molecules rescue the functional activity and agonist potency of dysfunctional human melanocortin-4 receptor polymorphismsZhimin Xiang
Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA
Biochemistry 46:8273-87. 2007..Thus, these ligands could generically rescue the potency and stimulatory response of the abnormally functioning hMC4Rs studied and may provide tools to further clarify the molecular mechanism(s) involving these receptor modifications...
- Common genetic variation near MC4R is associated with waist circumference and insulin resistanceJohn C Chambers
Department of Epidemiology and Public Health, Imperial College London, Norfolk Pl, London W2 1PG, UK
Nat Genet 40:716-8. 2008..Homozygotes for the risk allele of rs12970134 have approximately 2 cm increased waist circumference. Common genetic variation near MC4R is associated with risk of adiposity and insulin resistance...
- Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigreesFanny Stutzmann
Centre National de la Recherche Scientifique 8090, Institute of Biology, Pasteur Institute, Lille, France
Diabetes 57:2511-8. 2008..However, there is uncertainty regarding the degree of penetrance of this condition, and the putative impact of the environment on the development of obesity in MC4R mutation carriers is unknown...
- The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in womenLu Qi
Department of Nutrition, Harvard School of Public Health, Boston, MA02115, USA
Hum Mol Genet 17:3502-8. 2008..In addition, the SNP was related to greater long-term weight change and increased risk of diabetes in women...
- Variants near MC4R are associated with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 DanesDorit P Zobel
Steno Diabetes Center, Gentofte, Denmark
Diabetes 58:757-64. 2009..We examined rs17782313, rs17700633, rs12970134, rs477181, rs502933, and rs4450508 near MC4R for association with obesity-related quantitative traits, obesity, and type 2 diabetes in Danish individuals...
- Association of functionally significant Melanocortin-4 but not Melanocortin-3 receptor mutations with severe adult obesity in a large North American case-control studyMelissa A Calton
Diabetes Center, University of California San Francisco, San Francisco, CA 94143, USA
Hum Mol Genet 18:1140-7. 2009..However, our data suggest that MC3R mutations are not associated with severe obesity in this population...
- Replication and extension of genome-wide association study results for obesity in 4923 adults from northern SwedenFrida Renstrom
Department of Public Health and Clinical Medicine, Umea University Hospital, Umea, Sweden
Hum Mol Genet 18:1489-96. 2009..In summary, we have statistically replicated six of the previously associated obese-risk loci and our results suggest that the weight-inducing effects of these variants are explained largely by increased adipose accumulation...
- Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestryStruan F A Grant
Center for Applied Genomics, Abramson Research Center, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Obesity (Silver Spring) 17:1461-5. 2009..As such, variants 3' to the MC4R locus present on the genotyping platform utilized confer a similar magnitude of risk of obesity in white children as to their adult white counterparts but this observation did not extend to AAs...
- Key amino acid residues in the melanocortin-4 receptor for nonpeptide THIQ specific binding and signalingYingkui Yang
Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35205, USA
Regul Pept 155:46-54. 2009b>Melanocortin 4 receptor (MC4R) plays an important role in the regulation of food intake and glucose homeostasis...
- NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE ConsortiumNancy L Heard-Costa
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, United States of America
PLoS Genet 5:e1000539. 2009..Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity...
- Association of the MC4R V103I polymorphism with obesity: a Chinese case-control study and meta-analysis in 55,195 individualsDu Wang
Division of Maternal and Child Health, School of Public Health, Peking University Health Science Center, Beijing, China
Obesity (Silver Spring) 18:573-9. 2010..It provides significant evidence for the association in East Asian populations. Further large-scaled studies in East Asian populations are needed to validate the association...
- Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese populationKikuko Hotta
Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, Yokohama, Japan
J Hum Genet 54:727-31. 2009..v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann-Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium channel tetramerisation domain containing 15 (KCTD15)...
- Life course variations in the associations between FTO and MC4R gene variants and body sizeRebecca Hardy
MRC Unit for Lifelong Health and Ageing, Department of Epidemiology and Public Health, University College London, 33 Bedford Place, London, UK
Hum Mol Genet 19:545-52. 2010..Studies of the aetiology of obesity spanning different age groups may identify age-specific determinants of weight gain...
- Common variants near melanocortin 4 receptor are associated with general and visceral adiposity in European- and African-American youthGaifen Liu
Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
J Pediatr 156:598-605.e1. 2010Recent genome-wide association studies found common variants near the melanocortin 4 receptor gene associated with obesity...
- Genome-wide association of anthropometric traits in African- and African-derived populationsSun J Kang
Department of Biostatistics and Epidemiology, Case Western Reserve University, Cleveland, OH 44106, USA
Hum Mol Genet 19:2725-38. 2010..Meta-analysis of this data set with additional studies in African-ancestry populations will be helpful to improve power to detect novel associations...
- Weight loss after Roux-en-Y gastric bypass in obese patients heterozygous for MC4R mutationsIvy R Aslan
Department of Pediatrics, Division of Endocrinology, University of California San Francisco, San Francisco, CA 94143, USA
Obes Surg 21:930-4. 2011..Bariatric surgery is a successful treatment for severe obesity. The mechanisms of weight loss after bariatric surgery are not well understood...
- Melanocortin-4 receptor gene mutations in a Dutch cohort of obese childrenLinda van den Berg
Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands
Obesity (Silver Spring) 19:604-11. 2011..These patients are difficult to recognize in a clinical setting. We generated a list of all MC4R variants that were described in the literature so far, which can aid the interpretation of mutations found in a diagnostic setting...
- Identification and functional characterization of novel mutations in the melanocortin-4 receptorSigri Beckers
Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
Obes Facts 3:304-11. 2010..Melanocortin-4 receptor (MC4R) deficiency is the most common cause of monogenic obesity. In the present study, we screened the MC4R gene for mutations in a population of overweight and obese children and adolescents...
- Association study of MC4R with complex obesity and replication of the rs17782313 association signalSigri Beckers
Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium
Mol Genet Metab 103:71-5. 2011..In conclusion, we could replicate the previously reported association between rs17782313 and complex obesity. Furthermore, our data do not support the hypothesis that a SNP in MC4R causes the rs17782313 association signal...
- Implication of European-derived adiposity loci in African AmericansJ M Hester
Center for Diabetes Research, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
Int J Obes (Lond) 36:465-73. 2012..Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans...
- Melanocortin-4 receptor signaling is required for weight loss after gastric bypass surgeryIda J Hatoum
Massachusetts General Hospital, 149 13th Street, Room 8219, Charlestown, Massachusetts 02129, USA
J Clin Endocrinol Metab 97:E1023-31. 2012..Recent evidence indicates that RYGB effects weight loss through multiple physiological mechanisms, including changes in energy expenditure, food intake, food preference, and reward pathways...
- Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgeryMarion Valette
Paris 13 University, Sorbone Paris Cité, Nutritional Epidemiology Research Unit UMR U557 INSERM, U1125 Inra, CNAM, CRNH IdF, Bobigny, France
PLoS ONE 7:e48221. 2012..This is the first case-control study to show that MC4R mutations and polymorphisms do not affect weight loss and body composition over one year after bariatric surgery...
- Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variantsM G Hohenadel
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health NIH, Phoenix, AZ, USA
Int J Obes (Lond) 38:1068-74. 2014..In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown...
- Molecular cloning, expression, and gene localization of a fourth melanocortin receptorI Gantz
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109 0386
J Biol Chem 268:15174-9. 1993..Using the technique of fluorescent in situ hybridization, the gene encoding the melanocortin-4 receptor was localized to chromosome 18 (q21.3)...
- A frameshift mutation in human MC4R is associated with a dominant form of obesityC Vaisse
Nat Genet 20:113-4. 1998
- Functional characterization of mutations in melanocortin-4 receptor associated with human obesityG Ho
Department of Cell Biology, Parke Davis Pharmaceutical Research, Ann Arbor, Michigan 48105, USA
J Biol Chem 274:35816-22. 1999..Thus, unlike the obesity-associated MC4R truncation mutants, the polymorphisms of MC4R are unlikely to be contributors to human obesity...
- Molecular determinants of ligand binding to the human melanocortin-4 receptorY K Yang
Departments of General Surgery and Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
Biochemistry 39:14900-11. 2000..In addition, mutation of TM3 residue D122 or D126 decreased the binding affinity of hMC4R antagonist SHU 9119. These results provide further insight into the molecular determinants of hMC4R ligand binding...
- Molecular determinants of human melanocortin-4 receptor responsible for antagonist SHU9119 selective activityYingkui Yang
Department of Surgery, University of Alabama at Birmingham, Alabama 35233, USA
J Biol Chem 277:20328-35. 2002..This report provides the details of the molecular recognition of SHU9119 antagonism at hMC4R and shows that amino acid Leu(133) of hMC4R plays a key role in melanocortin receptor subtype specificity...
- Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutationsCecile Lubrano-Berthelier
Diabetes Center and Department of Medicine, University of California, San Francisco, CA 94143, USA
Hum Mol Genet 12:145-53. 2003Heterozygous mutations in the coding region of the serpentine Melanocortin 4 receptor are the most common genetic cause of human obesity described to date...
- Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesityWouter A J Nijenhuis
Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
J Biol Chem 278:22939-45. 2003..Hemagglutinin-tagged mutant receptors were retained in the intracellular environment. These pharmacological data provide a basis to estimate the quantitative effect of MC4R mutations for the development of obesity...
- Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese femalePatricia A Donohoue
Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
J Clin Endocrinol Metab 88:5841-5. 2003..We conclude that this novel mutation is the cause of obesity of this patient...
- Genetic screening for melanocortin-4 receptor mutations in a cohort of Italian obese patients: description and functional characterization of a novel mutationFerruccio Santini
Department of Endocrinology and Metabolism, University of Pisa, 56124 Pisa, Italy
J Clin Endocrinol Metab 89:904-8. 2004..7% prevalence of potentially pathogenic mutations. A novel heterozygous missense mutation (Glu(308)Lys) that impairs MC4-R functional activity in vitro was characterized...
- Melanocortin-4 receptor gene variant I103 is negatively associated with obesityFrank Geller
Institute of Medical Biometry and Epidemiology, Philipps University, Marburg, Germany
Am J Hum Genet 74:572-81. 2004..The respective protective effect against obesity implies that variation in the MC4R gene entails both loss and gain of function...
- The Val103Ile polymorphism of melanocortin-4 receptor regulates energy expenditure and weight gainJarno Rutanen
Department of Medicine, Kuopio University Hospital, PB 1777, 70211 Kuopio, Finland
Obes Res 12:1060-6. 2004..The melanocortin-4 receptor (MC4R) regulates energy intake. On the basis of animal studies, it may also regulate energy expenditure...
- Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesityNatascha Potoczna
Klinik Hirslanden, Witellikerstrasse, Zurich, Switzerland
J Gastrointest Surg 8:971-81; discussion 981-2. 2004..Overall outcome was poorest in MC4R variant carriers, better in noncarriers with BED (P < 0.05), and best in noncarriers without BED (P < 0.001). MC4R variants influence comorbidities and treatment outcomes in severe obesity...
- Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveysI M Heid
J Med Genet 42:e21. 2005..69, p = 0.03). However, evidence in a large population based study in a homogeneous population and a significant estimate of the change in quantitative measures of obesity is still lacking...
- Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern ItalyPasqualina Buono
Facoltà di Scienze Motorie, Università degli Studi Parthenope di Napoli, Naples, Italy
Clin Chem 51:1358-64. 2005..Here we report variants of the proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) genes detected in severely obese adults living in southern Italy.
- Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonistsIrina D Pogozheva
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, USA
Biochemistry 44:11329-41. 2005....
- Cart overexpression is the only identifiable cause of high bone mass in melanocortin 4 receptor deficiencyJong Deok Ahn
Department of Molecular and Human Genetics, One Baylor Plaza, Baylor College of Medicine, Houston, Texas 77030, USA
Endocrinology 147:3196-202. 2006..CART expression in the hypothalamus is increased in mice lacking melanocortin 4 receptor (Mc4r(-/-) mice)...
- The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individualsE H Young
MRC Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK
Int J Obes (Lond) 31:1437-41. 2007..Previous studies have suggested that a variant in the melanocortin-4 receptor (MC4R) gene is important in protecting against common obesity. Larger studies are needed, however, to confirm this relation...
- Contribution of the conserved amino acids of the melanocortin-4 receptor in [corrected] [Nle4,D-Phe7]-alpha-melanocyte-stimulating [corrected] hormone binding and signalingMin Chen
Department of Surgery and Nutrition, University of Alabama, Birmingham, AL 35205, USA
J Biol Chem 282:21712-9. 2007b>Melanocortin 4 receptor (MC4R) plays an important role in the regulation of food intake and body weight...
- Substituted NDP-MSH peptides paired with mutant melanocortin-4 receptors demonstrate the role of transmembrane 6 in receptor activationBeth A Fleck
Departments of Pharmacology, Neurocrine Biosciences Inc, 12790 El Camino Real, San Diego, California 92130, USA
Biochemistry 46:10473-83. 2007..51) and F284(7.35). These findings refine the molecular basis for the mechanism of ligand-stimulated hMC4R activation and will be useful for the development of hMC4R agonists and antagonists...
- Association of the MC4R V103I polymorphism with the metabolic syndrome: the KORA StudyIris M Heid
Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, Germany
Obesity (Silver Spring) 16:369-76. 2008..This study aims to provide epidemiological evidence for showing the association of this polymorphism with features of the metabolic syndrome and with parameters related to energy expenditure and dietary habits as potential mediators...
- Further evidence for the role of ENPP1 in obesity: association with morbid obesity in FinnsKaisa Valli-Jaakola
Department of Medicine and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland
Obesity (Silver Spring) 16:2113-9. 2008..In this study, we did not find association between the frequently studied ENPP1 K121Q variant, nor SNPs in the MCR or POMC genes and obesity or type 2 diabetes...
- Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptorKaren Tan
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Box 289, Hills Road, Cambridge CB2 2QQ, United Kingdom
Endocrinology 150:114-25. 2009Mutations in the melanocortin 4 receptor (MC4R) gene are the most common known cause of monogenic human obesity. The MC4R gene was sequenced in 2000 subjects with severe early-onset obesity...
- Lifestyle intervention in obese children with variations in the melanocortin 4 receptor geneThomas Reinehr
Department of Pediatric Nutrition Medicine, Vestische Hospital for Children and Adolescents Datteln, University of Witten Herdecke, Datteln, Germany
Obesity (Silver Spring) 17:382-9. 2009Because information on weight changes after lifestyle intervention in children with mutations in the melanocortin 4 receptor (MC4R) gene is scarce, we compared weight changes after lifestyle intervention between children with and without ..
- GPCR Variants as Genetic Determinants of ObesityAlan Kopin; Fiscal Year: 2009..In Aim 3, combinations of anorexigenic, orexigenic and hedonic receptor variants will be assessed as potential synergistic or additive factors underlying the polygenic basis of obesity and/or other Look AHEAD study endpoints. ..
- Melanocortin system stress and HPA axisXin Yun Lu; Fiscal Year: 2010....
- Endogenous G-Protein Coupled Receptor AntagonistsCarrie Haskell-Luevano; Fiscal Year: 2012..This research project proposes to generate knowledge for the rational design of molecules as potential therapeutic agents to prevent or treat the diseases associated with over or under eating. ..
- Development of allosteric modulators of the MC4 receptorJULIEN ALBERT SEBAG; Fiscal Year: 2011..The potential application of these compounds to common dietary obesity will also be examined. ..
- KRISTEN RACHEL VELLA; Fiscal Year: 2014..on the regulation of thyroid hormone levels by neuropeptide Y through the central thyroid axis and the melanocortin 4 receptor through hepatic thyroid hormone metabolism resulted in a 1st-author publication in Cell Metabolism...
- Qingchun Tong; Fiscal Year: 2016....
- Obesity is a Surgical ProblemMichael W Mulholland; Fiscal Year: 2013..We hypothesize that directed overexpression of Asb-4 in hypothalamic proopiomelanocortin neurons will decrease food intake, increase energy expenditure and confer resistance to high fat diet-induced obesity. ..
- Young Hwan Jo; Fiscal Year: 2016..Hence the proposed studies will provide novel insights into the neurobiology of melanocortin system in general and its specific role in the control of energy balance in particular. ..
- Lei Cao; Fiscal Year: 2016..genetically activating HSA axis by BDNF gene therapy can alleviate obesity and inhibit tumor growth in melanocortin receptor 4 (MC4R) deficient mice...
- Robert C Ritter; Fiscal Year: 2016..Detailed appreciation of NTS NMDAr contributions to control of food intake is of significance to human health because it may provide avenues for therapeutic intervention in eating disorders and obesity. ..
- Vincent Aguirre; Fiscal Year: 2014..abstract_text> ..
- Melanocortin-4 Receptor Traffic and SignalingGiulia Baldini; Fiscal Year: 2012..It is anticipated that these studies will broaden our understanding of traffic and signaling of MC4R and of obesity- linked variants and will help find new targets for therapies against obesity. ..
- Role of Sim1 in Hyperphagic ObesityBassil M Kublaoui; Fiscal Year: 2010..We are trying understand how the brain regulates our eating behavior. We study a gene that was found to cause morbid obesity in a girl. We are using a mouse model of this gene to understand how it causes obesity. ..
- MODULATION OF OLFACTORY BULB NEURON CURRENT PROPERTIESDebra Ann Fadool; Fiscal Year: 2013..3. Gene-targeted deletions of Kv1.3 channel protein and the melanocortin 4 receptor will provide mechanistic details of how this potassium channel regulates energy homeostasis that ..
- Yong Xu; Fiscal Year: 2015..Mouse models will be generated in which melanocortin 4 receptor (MC4R), the receptor for the POMC product, will be re-expressed in two distinct site of the brain at the ..
- Rudolph L Leibel; Fiscal Year: 2016..Success in this endeavor will impact diagnosis, treatment and prevention of obesity and its associated co-morbidities such as diabetes and heart disease. ..
- Roger D Cone; Fiscal Year: 2016..Finally, we will attempt to identify serum biomarkers for melanocortin signaling as a less invasive tool for analysis of allosteric modulators of melanocortin signaling. ..
- BRENT MATTHEW MOLDEN; Fiscal Year: 2014DESCRIPTION (provided by applicant): The Melanocortin Receptor 4 (MC4R) is a G-protein coupled receptor (GPCR) which is central to the control of appetite...
- Christian Vaisse; Fiscal Year: 2016..These experiments could lead to new strategies to pharmacologically target MC4R for the treatment of obesity. ..
- Carrie Haskell-Luevano; Fiscal Year: 2015..abstract_text> ..
- Brain Melanocortin Control of Activity Energy Expenditure and Obesity ResistanceColleen M Novak; Fiscal Year: 2013..Focusing on identifying unique features of central (brain) and peripheral (e.g., skeletal muscle) control of energy balance in the lean phenotype may yield novel treatments for obesity. ..
- Bradford B Lowell; Fiscal Year: 2016..In total, investigation of this distributed, interconnected, glutamatergic model of MC4R action should shed new light on neural circuits regulating food intake and energy balance. ..
- Jane F Reckelhoff; Fiscal Year: 2015..that contributes to SNS activation and increases BP by stimulating brain pro-opiomelanocortin pathway via melanocortin 4 receptor (MC4R) activation...
- Sim1 Function in Feeding RegulationAndrew R Zinn; Fiscal Year: 2013..abnormalities are also seen in mice with mutations that interfere with hypothalamic signaling via the melanocortin 4 receptor (MC4R), which is abundantly expressed in neurons within or projecting to the PVN...
- Sandra J Hasstedt; Fiscal Year: 2014....
- Functional Selectivity in MC4R SignalingTooraj Mirshahi; Fiscal Year: 2012..Mutations in the melanocortin 4 receptor (MC4R) are the most common form of monogenic obesity, found in 1-5% of obese people...
- KARL LEONARD INSOGNA; Fiscal Year: 2015..POMC) and its key derivate, 1-melanocyte stimulating hormone (1MSH), which is the agonist for the melanocortin 4 receptor (MC4R). Activation of MC4R receptors leads to satiety and increased sympathetic tone...
- Role of Pro-opiomelanocortin mutations in human obesityChristian Vaisse; Fiscal Year: 2007..unreadable] [unreadable]..
- The Role of the Central Melanocortin System in the Muscle Wasting of CachexiaTHEODORE PAUL BRAUN; Fiscal Year: 2013..b>Melanocortin 4 receptor (MC4R) knockout mice have an increased lean mass phenotype, and are resistant to loss of lean mass in ..
- Regulation of Glucagon Secretion by Melanocortin Receptor-4Joseph K Angleson; Fiscal Year: 2010..The proposed studies seek to identify a major point of control of alpha cell function. ..
- Leptin as a regular of bone massGerard Karsenty; Fiscal Year: 2010..To determine, in vivo, the role of CREB as a transcriptional mediator of the leptin-dependent sympathetic regulation of bone mass. - To establish in vivo the role of c-myc as a mediator of the clock genes regulation of bone formation. ..
- Molecular control of melanocortin receptor signalingGlenn L Millhauser; Fiscal Year: 2013..Analogous strategies will be used with members of the 2-defensin family to advance the understanding of the defensin fold and to produce useful protein for pharmacological and structural studies. ..
- Fifth International Melanocortin MeetingROGER CONE; Fiscal Year: 2002..To facilitate the gathering of a large international audience, funds are specifically requested to cover travel expenses for 17 speakers. ..
- Novel Melanocortin Receptor 4 Agonist for ObesityLiang Cao; Fiscal Year: 2003..key components of this system include neuropeptide melanocortin and its G-protein coupled receptor, the melanocortin receptor 4 (MC4R)...
- Distributed neural control of energy expenditureMatthew Hayes; Fiscal Year: 2009....
- Todd E Thiele; Fiscal Year: 2014..The work that is outlined in the current proposal will show that melanocortin neuropeptides modulate the reinforcing properties of alcohol and relapse of alcohol-seeking behavior following abstinence. ..
- Regulation of food intake by melanocortin 4 receptors on neurons of the PVNLinh Vong; Fiscal Year: 2009The melanocortin 4 receptor (MC4R) has been shown to be an important regulator of energy homeostasis in both rodents and humans by decreasing food intake and increasing energy expenditure...
- Functional Neuroanatomy of Cytokine-Mediated AnorexiaTeresa Reyes; Fiscal Year: 2007..At the conclusion of these studies, the candidate will be well positioned to obtain an independent academic research position. ..
- Human Melanocortin-4 Receptor PolymorphismsCarrie Haskell Luevano; Fiscal Year: 2007..Understanding obesity related mechanisms may ultimately result in therapeutic agents to prevent or treat the diseases associated with over eating. ..
- STRUCTURAL DETERMINANTS OF NEUROENDOCRINE RECEPTORSCarrie Haskell Luevano; Fiscal Year: 2008..abstract_text> ..
- Molecular determinants of melanocortin 4 receptor for selective agonist bindingYingkui Yang; Fiscal Year: 2009..This R03 application is to explore the molecular basis of melanocorin 4 receptor responsible for agonist activity which can be used to develop new therapuetic approach for obesity. ..
- Molecular determinants of ACTH receptor for ligand bindingYingkui Yang; Fiscal Year: 2006..The information will serve to establish a foundation on which to build a comprehensive understanding of the signaling events that regulate ACTH mediated adrenal function in physiologic and diseased states. ..
- Peptide Hormone Structure FunctionVictor J Hruby; Fiscal Year: 2010....
- Melanocortin-3 receptor regulation of insulin actionAndrew Butler; Fiscal Year: 2005..The results of these experiments will provide the first definitive evidence that manipulation of the MC3R might be a viable approach for treating insulin resistance. ..
- Molecular mechanism of G protein coupling to the melanocortin-3 receptorYa Xiong Tao; Fiscal Year: 2008..Current pharmacotherapies are far from ideal in terms of both efficacy and side effect. Our long-term goal is to exploit the melanocortin system as a novel approach for obesity treatment. [unreadable] [unreadable] [unreadable]..
- Physiology and genetics of food procurement in rodentsNeil Rowland; Fiscal Year: 2008..economy protocol, is to test whether mice either heterozygous or homozygous for genetic deletion of melanocortin 4 receptor deletion exhibit altered meal patterns or elasticity of food demand compared with wild type controls...
- Cue dependency with intravenous nutrients and nicotineNeil Rowland; Fiscal Year: 2007..These studies may help to develop ways in conditioned preferences can be manipulated to prevent or treat certain addictive disorders, including overeating. [unreadable] [unreadable] [unreadable]..
- CHRONIC OBSTRUCTIVE PULMONARY DISEASE GENE LOCALIZATIONSANDRA HASSTEDT; Fiscal Year: 2002..Identifying a gene that when mutated increases the risk of COPD may increase understanding of pulmonary function, as well as allowing gene-carriers to be identified and made aware of their susceptibility. ..
- Sympathetic Ganglia: New Target for ACTH with StressEsther Sabban; Fiscal Year: 2008..abstract_text> ..
- MOLECULAR BIOLOGY OF NOREPINEPHRINE BIOSYNTHESISEsther Sabban; Fiscal Year: 2006..These findings will contribute to the development of new strategies to prevent the harmful maladaptive changes in catecholamine neurotransmission, while enhancing its beneficial adaptive aspects ..
- MODELS FOR THE GENETIC EPIDEMIOLOGY OF CHRONIC DISEASESANDRA HASSTEDT; Fiscal Year: 2009..In addition, this application proposes to implement changes to increase computational speed, allow data exploration, and facilitate data handling and analysis, while continuing to distribute and support PAP. ..
- The Role of Serotonin in Energy Homeostasis in C. elegansSupriya Srinivasan; Fiscal Year: 2008..The ancient conservation of serotonin function in many species including mice and humans suggests that work proposed here will provide novel genetic targets for the study of body fat regulation. [unreadable] [unreadable]..
- ENTEROSTATIN REGULATION OF FAT INTAKEDavid York; Fiscal Year: 2005..Fourth they will identify the neuropathways responsive to enterostatin by immunohistochemistry and tract tracing techniques. Finally these pathway responsiveness to dietary fat will be evaluated. ..
- The Family Blood Pressure Program (HyperGEN Network)Steven Hunt; Fiscal Year: 2007..unreadable] (End of Abstract) [unreadable] [unreadable]..
- GENETIC EPIDEMIOLOGY OF AGING IN UTAH PEDIGREESSteven Hunt; Fiscal Year: 2007..This collection of longitudinally followed pedigrees provides a powerful study design to address a wide range of genetic epidemiological analyses of aging. ..
- Attractin and Mahoganoid in Spongy NeurodegenerationGregory Barsh; Fiscal Year: 2007..Investigating the biochemical, cellular, and genetic relationships between Atrn, Mahoganoid, and PrP is likely to provide general insight into the pathogenesis of spongy degeneration. [unreadable] [unreadable]..
- Genetics of Dark Skin in MiceGregory Barsh; Fiscal Year: 2006..unreadable] [unreadable]..
- Metabolic regulation of midbrain dopamine neuronsRobert MacKenzie; Fiscal Year: 2005..Completion of the project will provide the necessary tools for a second phase project in which specific genes will be examined for their role in mediating the direct or indirect action of leptin on midbrain DA neurons. ..
- MULTIPLE SEVERE OBESITY RISK GENES IN UTAH PEDIGREESSteven Hunt; Fiscal Year: 2009..Validation will be tested in a large case/control series, Polynesian families, and, for chromosome 20, in the congenic mouse model. ..
- GENCAC - Utah Field CenterSteven Hunt; Fiscal Year: 2004..abstract_text> ..
- CONTAINMENT FACILITIES FOR NUTRITIONAL RESEARCHDavid York; Fiscal Year: 2004..abstract_text> ..
- CLINICAL TRIALS IN SCHIZOPHRENIA--MOLECULAR APPROACHESAnil Malhotra; Fiscal Year: 2003..abstract_text> ..
- REGULATION OF ENERGY BALANCE BY MELANOCORTIN ANTAGONISTSGregory Barsh; Fiscal Year: 2003..abstract_text> ..
- Microarray analysis of identified neurons in the brainRobert MacKenzie; Fiscal Year: 2002..It is expected that the completion of this Phase I proposal will result in a reliable and flexible discovery platform. Deployment of the approach for new target discovery will occur in Phase II. ..