melanocortin 4 receptor

Summary

Gene Symbol: melanocortin 4 receptor
Description: melanocortin 4 receptor
Alias: melanocortin receptor 4, MC4-R
Species: human

Top Publications

  1. ncbi A frameshift mutation in MC4R associated with dominantly inherited human obesity
    G S Yeo
    Nat Genet 20:111-2. 1998
  2. pmc Common variants near MC4R are associated with fat mass, weight and risk of obesity
    Ruth J F Loos
    MRC Epidemiology Unit, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
    Nat Genet 40:768-75. 2008
  3. ncbi Functional analyses of melanocortin-4 receptor mutations identified from patients with binge eating disorder and nonobese or obese subjects
    Ya 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
  4. ncbi Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene
    I Sadaf Farooqi
    University Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 348:1085-95. 2003
  5. ncbi Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain
    K G Mountjoy
    Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201 3098
    Mol Endocrinol 8:1298-308. 1994
  6. doi Combined effects of FTO rs9939609 and MC4R rs17782313 on obesity and BMI in Chinese Han populations
    Wei Huang
    Division of Endocrinology, Department of Puren Hospital, Wuhan University of Science and Technology, Wuhan, China
    Endocrine 39:69-74. 2011
  7. doi Mutations in melanocortin-4 receptor and human obesity
    Ya 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
  8. pmc Investigation of a genome wide association signal for obesity: synthetic association and haplotype analyses at the melanocortin 4 receptor gene locus
    Andre Scherag
    Institute of Medical Informatics, Biometry and Epidemiology, University of Duisburg Essen, Essen, Germany
    PLoS ONE 5:e13967. 2010
  9. ncbi Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating
    Cecile 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
  10. pmc Evaluation of genetic susceptibility loci for obesity in Chinese women
    Jiajun Shi
    Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Am J Epidemiol 172:244-54. 2010

Research Grants

  1. GPCR Variants as Genetic Determinants of Obesity
    Alan Kopin; Fiscal Year: 2009
  2. Melanocortin system stress and HPA axis
    Xin Yun Lu; Fiscal Year: 2010
  3. Endogenous G-Protein Coupled Receptor Antagonists
    Carrie Haskell-Luevano; Fiscal Year: 2012
  4. Development of allosteric modulators of the MC4 receptor
    JULIEN ALBERT SEBAG; Fiscal Year: 2011
  5. KRISTEN RACHEL VELLA; Fiscal Year: 2014
  6. Qingchun Tong; Fiscal Year: 2016
  7. Obesity is a Surgical Problem
    Michael W Mulholland; Fiscal Year: 2013
  8. Young Hwan Jo; Fiscal Year: 2016
  9. Lei Cao; Fiscal Year: 2016
  10. Robert C Ritter; Fiscal Year: 2016

Detail Information

Publications256 found, 100 shown here

  1. ncbi A frameshift mutation in MC4R associated with dominantly inherited human obesity
    G S Yeo
    Nat Genet 20:111-2. 1998
  2. pmc Common variants near MC4R are associated with fat mass, weight and risk of obesity
    Ruth J F Loos
    MRC Epidemiology Unit, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
    Nat Genet 40:768-75. 2008
    ....
  3. ncbi Functional analyses of melanocortin-4 receptor mutations identified from patients with binge eating disorder and nonobese or obese subjects
    Ya 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...
  4. ncbi Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene
    I Sadaf Farooqi
    University Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 348:1085-95. 2003
    b>Melanocortin 4 receptor (MC4R) deficiency is the commonest monogenic form of obesity...
  5. ncbi Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain
    K 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...
  6. doi Combined effects of FTO rs9939609 and MC4R rs17782313 on obesity and BMI in Chinese Han populations
    Wei 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...
  7. doi Mutations in melanocortin-4 receptor and human obesity
    Ya 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...
  8. pmc Investigation of a genome wide association signal for obesity: synthetic association and haplotype analyses at the melanocortin 4 receptor gene locus
    Andre 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)...
  9. ncbi Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating
    Cecile 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...
  10. pmc Evaluation of genetic susceptibility loci for obesity in Chinese women
    Jiajun 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...
  11. doi Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations
    David 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))...
  12. doi Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study
    Y 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...
  13. doi Common polymorphism near the MC4R gene is associated with type 2 diabetes: data from a meta-analysis of 123,373 individuals
    B 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. 2012
    Genome-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...
  14. pmc Lower metabolic rate in individuals heterozygous for either a frameshift or a functional missense MC4R variant
    Jonathan Krakoff
    Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, Phoenix, AZ, USA
    Diabetes 57:3267-72. 2008
    Humans 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.
  15. ncbi The human intronless melanocortin 4-receptor gene is NMD insensitive
    Katja 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...
  16. ncbi Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalization
    Hiroshi 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...
  17. ncbi Molecular mechanism of the constitutive activation of the L250Q human melanocortin-4 receptor polymorphism
    Bettina Proneth
    Department of Medicinal Chemistry, University of Florida, PO Box 100485, Gainesville, FL 32610 0485, USA
    Chem Biol Drug Des 67:215-29. 2006
    ....
  18. ncbi A two-base deletion -439delGC in the melanocortin-4 receptor promoter associated with early-onset obesity
    Kaisa 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...
  19. pmc Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesity
    Nicola 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...
  20. pmc Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family Study
    Y C Chagnon
    Physical Activity Sciences Laboratory, Laval University, Ste Foy, Quebec, Canada
    Mol Med 3:663-73. 1997
    ....
  21. ncbi High affinity agonistic metal ion binding sites within the melanocortin 4 receptor illustrate conformational change of transmembrane region 3
    Malin C Lagerström
    Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden
    J Biol Chem 278:51521-6. 2003
    We 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...
  22. pmc Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans
    Supriya 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...
  23. ncbi Obesity and eating behaviour in a three-generation Chilean family with carriers of the Thrl50Ile mutation in the melanocortin-4 receptor gene
    J L Santos
    Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Catolica de Chile
    J Physiol Biochem 64:205-10. 2008
    It 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...
  24. doi Mutations in the melanocortin 4 receptor (MC4R) gene in obese patients in Norway
    T Wangensteen
    Department of Medical Genetics, Ulleval University Hospital, Oslo, Norway
    Exp Clin Endocrinol Diabetes 117:266-73. 2009
    Mutations 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%.
  25. doi Replication of association between a common variant near melanocortin-4 receptor gene and obesity-related traits in Asian Sikhs
    Latonya 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...
  26. doi 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 efficacy
    R Krishna
    Merck and Co, Inc, Whitehouse Station, New Jersey, USA
    Clin Pharmacol Ther 86:659-66. 2009
    MK-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...
  27. ncbi Melanocortin 4 receptor mutations in obese Czech children: studies of prevalence, phenotype development, weight reduction response, and functional analysis
    Irena 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. 2007
    Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common known cause of monogenic human obesity.
  28. doi 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) Study
    Eryn 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...
  29. pmc Genes and lifestyle factors in obesity: results from 12,462 subjects from MONICA/KORA
    C 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...
  30. pmc Obesity-linked variants of melanocortin-4 receptor are misfolded in the endoplasmic reticulum and can be rescued to the cell surface by a chemical chaperone
    Susana 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...
  31. ncbi Melanocortin-4 receptor mutations in obesity
    Ferruccio Santini
    Department of Endocrinology and Kidney, University Hospital of Pisa, 56124 Pisa, Italy
    Adv Clin Chem 48:95-109. 2009
    ....
  32. ncbi A novel nonsense mutation in the melanocortin-4 receptor associated with obesity in a Spanish population
    A 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.
  33. ncbi Functional characterization of melanocortin-4 receptor mutations associated with childhood obesity
    Ya 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...
  34. ncbi A homozygous null mutation delineates the role of the melanocortin-4 receptor in humans
    Cecile 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...
  35. pmc Engineering the melanocortin-4 receptor to control constitutive and ligand-mediated G(S) signaling in vivo
    Supriya 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...
  36. ncbi Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans
    A 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...
  37. ncbi Identification of domains directing specificity of coupling to G-proteins for the melanocortin MC3 and MC4 receptors
    Chung 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...
  38. ncbi A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism
    Benjamin 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...
  39. ncbi Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort
    Peter Jacobson
    Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808, USA
    J Clin Endocrinol Metab 87:4442-6. 2002
    The 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,..
  40. ncbi Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms
    Giles 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
    ....
  41. ncbi 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...
  42. ncbi Identification and characterization of melanocortin-4 receptor gene mutations in morbidly obese finnish children and adults
    Kaisa 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...
  43. ncbi Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population
    Rong 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...
  44. ncbi Role of third intracellular loop of the melanocortin 4 receptor in the regulation of constitutive activity
    Do 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. 2008
    The melanocortin 4 receptor (MC4R) has been reported to display constitutive activity, which is probably relevant to the maintenance of a normal energy balance...
  45. doi Common genetic variation near MC4R is associated with eating behaviour patterns in European populations
    F 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...
  46. ncbi Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity
    E 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...
  47. ncbi Binge eating as a major phenotype of melanocortin 4 receptor gene mutations
    Ruth 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.
  48. ncbi 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 obesity
    Anke 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...
  49. ncbi Modeling and docking of the three-dimensional structure of the human melanocortin 4 receptor
    Xiaonan Yang
    Laboratory of Bioinformatics, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
    J Protein Chem 22:335-44. 2003
    A 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)...
  50. ncbi Mutationally induced disulfide bond formation within the third extracellular loop causes melanocortin 4 receptor inactivation in patients with obesity
    Patrick 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. 2003
    By 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...
  51. ncbi Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations
    J 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...
  52. ncbi Melanocortin 4 receptor gene variation is associated with severe obesity in Pima Indians
    Lijun 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. 2004
    Heterozygous coding mutations in the melanocortin 4 receptor gene (MC4R) are the most common genetic causes of severe human obesity identified to date...
  53. pmc Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index
    A Dempfle
    J Med Genet 41:795-800. 2004
  54. ncbi Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity
    Lesli 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. 2005
    Mutations 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...
  55. ncbi Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene
    Fanny 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...
  56. ncbi Peptide and small molecules rescue the functional activity and agonist potency of dysfunctional human melanocortin-4 receptor polymorphisms
    Zhimin 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...
  57. doi Common genetic variation near MC4R is associated with waist circumference and insulin resistance
    John 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...
  58. pmc Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees
    Fanny 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...
  59. pmc The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women
    Lu 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...
  60. pmc Variants near MC4R are associated with obesity and influence obesity-related quantitative traits in a population of middle-aged people: studies of 14,940 Danes
    Dorit 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...
  61. pmc Association of functionally significant Melanocortin-4 but not Melanocortin-3 receptor mutations with severe adult obesity in a large North American case-control study
    Melissa 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...
  62. pmc Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden
    Frida 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...
  63. pmc Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry
    Struan 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...
  64. pmc Key amino acid residues in the melanocortin-4 receptor for nonpeptide THIQ specific binding and signaling
    Yingkui Yang
    Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35205, USA
    Regul Pept 155:46-54. 2009
    b>Melanocortin 4 receptor (MC4R) plays an important role in the regulation of food intake and glucose homeostasis...
  65. pmc NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium
    Nancy 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...
  66. doi Association of the MC4R V103I polymorphism with obesity: a Chinese case-control study and meta-analysis in 55,195 individuals
    Du 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...
  67. doi Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population
    Kikuko 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)...
  68. pmc Life course variations in the associations between FTO and MC4R gene variants and body size
    Rebecca 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...
  69. pmc Common variants near melanocortin 4 receptor are associated with general and visceral adiposity in European- and African-American youth
    Gaifen 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. 2010
    Recent genome-wide association studies found common variants near the melanocortin 4 receptor gene associated with obesity...
  70. pmc Genome-wide association of anthropometric traits in African- and African-derived populations
    Sun 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...
  71. pmc Weight loss after Roux-en-Y gastric bypass in obese patients heterozygous for MC4R mutations
    Ivy 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...
  72. doi Melanocortin-4 receptor gene mutations in a Dutch cohort of obese children
    Linda 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...
  73. doi Identification and functional characterization of novel mutations in the melanocortin-4 receptor
    Sigri 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...
  74. doi Association study of MC4R with complex obesity and replication of the rs17782313 association signal
    Sigri 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...
  75. pmc Implication of European-derived adiposity loci in African Americans
    J 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...
  76. pmc Melanocortin-4 receptor signaling is required for weight loss after gastric bypass surgery
    Ida 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...
  77. pmc Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery
    Marion 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...
  78. pmc Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants
    M 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...
  79. ncbi Molecular cloning, expression, and gene localization of a fourth melanocortin receptor
    I 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)...
  80. ncbi A frameshift mutation in human MC4R is associated with a dominant form of obesity
    C Vaisse
    Nat Genet 20:113-4. 1998
  81. ncbi Functional characterization of mutations in melanocortin-4 receptor associated with human obesity
    G 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...
  82. ncbi Molecular determinants of ligand binding to the human melanocortin-4 receptor
    Y 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...
  83. ncbi Molecular determinants of human melanocortin-4 receptor responsible for antagonist SHU9119 selective activity
    Yingkui 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...
  84. ncbi Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations
    Cecile Lubrano-Berthelier
    Diabetes Center and Department of Medicine, University of California, San Francisco, CA 94143, USA
    Hum Mol Genet 12:145-53. 2003
    Heterozygous mutations in the coding region of the serpentine Melanocortin 4 receptor are the most common genetic cause of human obesity described to date...
  85. ncbi Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity
    Wouter 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...
  86. ncbi Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female
    Patricia 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...
  87. ncbi Genetic screening for melanocortin-4 receptor mutations in a cohort of Italian obese patients: description and functional characterization of a novel mutation
    Ferruccio 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...
  88. pmc Melanocortin-4 receptor gene variant I103 is negatively associated with obesity
    Frank 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...
  89. ncbi The Val103Ile polymorphism of melanocortin-4 receptor regulates energy expenditure and weight gain
    Jarno 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...
  90. ncbi Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesity
    Natascha 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...
  91. pmc Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys
    I 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...
  92. ncbi Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy
    Pasqualina 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.
  93. pmc Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists
    Irina D Pogozheva
    Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, USA
    Biochemistry 44:11329-41. 2005
    ....
  94. ncbi Cart overexpression is the only identifiable cause of high bone mass in melanocortin 4 receptor deficiency
    Jong 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)...
  95. pmc The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals
    E 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...
  96. pmc Contribution of the conserved amino acids of the melanocortin-4 receptor in [corrected] [Nle4,D-Phe7]-alpha-melanocyte-stimulating [corrected] hormone binding and signaling
    Min Chen
    Department of Surgery and Nutrition, University of Alabama, Birmingham, AL 35205, USA
    J Biol Chem 282:21712-9. 2007
    b>Melanocortin 4 receptor (MC4R) plays an important role in the regulation of food intake and body weight...
  97. ncbi Substituted NDP-MSH peptides paired with mutant melanocortin-4 receptors demonstrate the role of transmembrane 6 in receptor activation
    Beth 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...
  98. doi Association of the MC4R V103I polymorphism with the metabolic syndrome: the KORA Study
    Iris 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...
  99. doi Further evidence for the role of ENPP1 in obesity: association with morbid obesity in Finns
    Kaisa 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...
  100. pmc Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptor
    Karen 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. 2009
    Mutations 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...
  101. doi Lifestyle intervention in obese children with variations in the melanocortin 4 receptor gene
    Thomas 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. 2009
    Because 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 ..

Research Grants65

  1. GPCR Variants as Genetic Determinants of Obesity
    Alan 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. ..
  2. Melanocortin system stress and HPA axis
    Xin Yun Lu; Fiscal Year: 2010
    ....
  3. Endogenous G-Protein Coupled Receptor Antagonists
    Carrie 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. ..
  4. Development of allosteric modulators of the MC4 receptor
    JULIEN ALBERT SEBAG; Fiscal Year: 2011
    ..The potential application of these compounds to common dietary obesity will also be examined. ..
  5. 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...
  6. Qingchun Tong; Fiscal Year: 2016
    ....
  7. Obesity is a Surgical Problem
    Michael 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. ..
  8. 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. ..
  9. 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...
  10. 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. ..
  11. Vincent Aguirre; Fiscal Year: 2014
    ..abstract_text> ..
  12. Melanocortin-4 Receptor Traffic and Signaling
    Giulia 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. ..
  13. Role of Sim1 in Hyperphagic Obesity
    Bassil 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. ..
  14. MODULATION OF OLFACTORY BULB NEURON CURRENT PROPERTIES
    Debra 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 ..
  15. 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 ..
  16. 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. ..
  17. 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. ..
  18. BRENT MATTHEW MOLDEN; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): The Melanocortin Receptor 4 (MC4R) is a G-protein coupled receptor (GPCR) which is central to the control of appetite...
  19. Christian Vaisse; Fiscal Year: 2016
    ..These experiments could lead to new strategies to pharmacologically target MC4R for the treatment of obesity. ..
  20. Carrie Haskell-Luevano; Fiscal Year: 2015
    ..abstract_text> ..
  21. Brain Melanocortin Control of Activity Energy Expenditure and Obesity Resistance
    Colleen 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. ..
  22. 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. ..
  23. 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...
  24. Sim1 Function in Feeding Regulation
    Andrew 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...
  25. Sandra J Hasstedt; Fiscal Year: 2014
    ....
  26. Functional Selectivity in MC4R Signaling
    Tooraj 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...
  27. 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...
  28. Role of Pro-opiomelanocortin mutations in human obesity
    Christian Vaisse; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  29. The Role of the Central Melanocortin System in the Muscle Wasting of Cachexia
    THEODORE 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 ..
  30. Regulation of Glucagon Secretion by Melanocortin Receptor-4
    Joseph K Angleson; Fiscal Year: 2010
    ..The proposed studies seek to identify a major point of control of alpha cell function. ..
  31. Leptin as a regular of bone mass
    Gerard 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. ..
  32. Molecular control of melanocortin receptor signaling
    Glenn 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. ..
  33. Fifth International Melanocortin Meeting
    ROGER CONE; Fiscal Year: 2002
    ..To facilitate the gathering of a large international audience, funds are specifically requested to cover travel expenses for 17 speakers. ..
  34. Novel Melanocortin Receptor 4 Agonist for Obesity
    Liang Cao; Fiscal Year: 2003
    ..key components of this system include neuropeptide melanocortin and its G-protein coupled receptor, the melanocortin receptor 4 (MC4R)...
  35. Distributed neural control of energy expenditure
    Matthew Hayes; Fiscal Year: 2009
    ....
  36. 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. ..
  37. Regulation of food intake by melanocortin 4 receptors on neurons of the PVN
    Linh Vong; Fiscal Year: 2009
    The 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...
  38. Functional Neuroanatomy of Cytokine-Mediated Anorexia
    Teresa Reyes; Fiscal Year: 2007
    ..At the conclusion of these studies, the candidate will be well positioned to obtain an independent academic research position. ..
  39. Human Melanocortin-4 Receptor Polymorphisms
    Carrie 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. ..
  40. STRUCTURAL DETERMINANTS OF NEUROENDOCRINE RECEPTORS
    Carrie Haskell Luevano; Fiscal Year: 2008
    ..abstract_text> ..
  41. Molecular determinants of melanocortin 4 receptor for selective agonist binding
    Yingkui 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. ..
  42. Molecular determinants of ACTH receptor for ligand binding
    Yingkui 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. ..
  43. Peptide Hormone Structure Function
    Victor J Hruby; Fiscal Year: 2010
    ....
  44. Melanocortin-3 receptor regulation of insulin action
    Andrew 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. ..
  45. Molecular mechanism of G protein coupling to the melanocortin-3 receptor
    Ya 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]..
  46. Physiology and genetics of food procurement in rodents
    Neil 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...
  47. Cue dependency with intravenous nutrients and nicotine
    Neil 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]..
  48. CHRONIC OBSTRUCTIVE PULMONARY DISEASE GENE LOCALIZATION
    SANDRA 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. ..
  49. Sympathetic Ganglia: New Target for ACTH with Stress
    Esther Sabban; Fiscal Year: 2008
    ..abstract_text> ..
  50. MOLECULAR BIOLOGY OF NOREPINEPHRINE BIOSYNTHESIS
    Esther 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 ..
  51. MODELS FOR THE GENETIC EPIDEMIOLOGY OF CHRONIC DISEASE
    SANDRA 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. ..
  52. The Role of Serotonin in Energy Homeostasis in C. elegans
    Supriya 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]..
  53. ENTEROSTATIN REGULATION OF FAT INTAKE
    David 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. ..
  54. The Family Blood Pressure Program (HyperGEN Network)
    Steven Hunt; Fiscal Year: 2007
    ..unreadable] (End of Abstract) [unreadable] [unreadable]..
  55. GENETIC EPIDEMIOLOGY OF AGING IN UTAH PEDIGREES
    Steven 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. ..
  56. Attractin and Mahoganoid in Spongy Neurodegeneration
    Gregory 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]..
  57. Genetics of Dark Skin in Mice
    Gregory Barsh; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  58. Metabolic regulation of midbrain dopamine neurons
    Robert 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. ..
  59. MULTIPLE SEVERE OBESITY RISK GENES IN UTAH PEDIGREES
    Steven 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. ..
  60. GENCAC - Utah Field Center
    Steven Hunt; Fiscal Year: 2004
    ..abstract_text> ..
  61. CONTAINMENT FACILITIES FOR NUTRITIONAL RESEARCH
    David York; Fiscal Year: 2004
    ..abstract_text> ..
  62. CLINICAL TRIALS IN SCHIZOPHRENIA--MOLECULAR APPROACHES
    Anil Malhotra; Fiscal Year: 2003
    ..abstract_text> ..
  63. REGULATION OF ENERGY BALANCE BY MELANOCORTIN ANTAGONISTS
    Gregory Barsh; Fiscal Year: 2003
    ..abstract_text> ..
  64. Microarray analysis of identified neurons in the brain
    Robert 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. ..