pro opiomelanocortin

Summary

Summary: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin.

Top Publications

  1. ncbi Targeted disruption of the melanocortin-4 receptor results in obesity in mice
    D Huszar
    Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    Cell 88:131-41. 1997
  2. ncbi Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA
    Miguel Lopez
    Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, U K
    Diabetes 55:1327-36. 2006
  3. ncbi Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis
    Nina Balthasar
    Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue RN, Boston, MA 02215, USA
    Neuron 42:983-91. 2004
  4. ncbi Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus
    M W Schwartz
    Department of Medicine, University of Washington, Pugent Sound VA Health Care System, Seattle 98108, USA
    Diabetes 46:2119-23. 1997
  5. pmc Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects
    Xiaorong Zhu
    Department of Biochemistry and Molecular Biology, University of Chicago, and the Howard Hughes Medical Institute, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 99:10293-8. 2002
  6. ncbi Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
    M A Cowley
    The Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA
    Nature 411:480-4. 2001
  7. pmc Immune cell-derived beta-endorphin. Production, release, and control of inflammatory pain in rats
    P J Cabot
    Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21287 8711, USA
    J Clin Invest 100:142-8. 1997
  8. ncbi Role of proopiomelanocortin neurons and peptides in the regulation of energy homeostasis
    M J Low
    Vollum Institute, Department of Behavioral Neuroscience, and Center for the Study of Weight Regulation and Associated Disorders, Oregon Health and Science University, Portland, OR 97239 3098, USA
    J Endocrinol Invest 27:95-100. 2004
  9. ncbi Transgenic neuronal expression of proopiomelanocortin attenuates hyperphagic response to fasting and reverses metabolic impairments in leptin-deficient obese mice
    Tooru M Mizuno
    Fishberg Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Diabetes 52:2675-83. 2003
  10. pmc Localization of p24 putative cargo receptors in the early secretory pathway depends on the biosynthetic activity of the cell
    R P Kuiper
    Department of Animal Physiology, Nijmegen Center for Molecular Life Sciences, University of Nijmegen, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
    Biochem J 360:421-9. 2001

Detail Information

Publications260 found, 100 shown here

  1. ncbi Targeted disruption of the melanocortin-4 receptor results in obesity in mice
    D Huszar
    Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    Cell 88:131-41. 1997
    ..Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R...
  2. ncbi Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA
    Miguel Lopez
    Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, U K
    Diabetes 55:1327-36. 2006
    ..The finding that TMX can modulate appetite through alterations in FAS expression and malonyl-CoA levels suggests a link between hypothalamic sex steroid receptors, fatty acid metabolism, and feeding behavior...
  3. ncbi Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis
    Nina Balthasar
    Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue RN, Boston, MA 02215, USA
    Neuron 42:983-91. 2004
    ..In summary, leptin receptors on POMC neurons are required but not solely responsible for leptin's regulation of body weight homeostasis...
  4. ncbi Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus
    M W Schwartz
    Department of Medicine, University of Washington, Pugent Sound VA Health Care System, Seattle 98108, USA
    Diabetes 46:2119-23. 1997
    ..These findings support the hypothesis that leptin signaling in the brain involves activation of the hypothalamic melanocortin system...
  5. pmc Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects
    Xiaorong Zhu
    Department of Biochemistry and Molecular Biology, University of Chicago, and the Howard Hughes Medical Institute, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 99:10293-8. 2002
    ..The PC1/3-null mice are not obese. The basis for these phenotypic differences is an interesting topic for further study. These findings prove the importance of PC1/3 as a key neuroendocrine convertase...
  6. ncbi Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
    M A Cowley
    The Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA
    Nature 411:480-4. 2001
    ..On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus...
  7. pmc Immune cell-derived beta-endorphin. Production, release, and control of inflammatory pain in rats
    P J Cabot
    Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland 21287 8711, USA
    J Clin Invest 100:142-8. 1997
    ..Thus, the immune system is important for the control of inflammatory pain. This has implications for the understanding of pain in immunosuppressed conditions like cancer or AIDS...
  8. ncbi Role of proopiomelanocortin neurons and peptides in the regulation of energy homeostasis
    M J Low
    Vollum Institute, Department of Behavioral Neuroscience, and Center for the Study of Weight Regulation and Associated Disorders, Oregon Health and Science University, Portland, OR 97239 3098, USA
    J Endocrinol Invest 27:95-100. 2004
    ..Both melanocortin peptides and the opioid beta-endorphin processed from POMC mediate the homeostatic and behavioral responses linked to POMC neuronal circuits...
  9. ncbi Transgenic neuronal expression of proopiomelanocortin attenuates hyperphagic response to fasting and reverses metabolic impairments in leptin-deficient obese mice
    Tooru M Mizuno
    Fishberg Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Diabetes 52:2675-83. 2003
    ....
  10. pmc Localization of p24 putative cargo receptors in the early secretory pathway depends on the biosynthetic activity of the cell
    R P Kuiper
    Department of Animal Physiology, Nijmegen Center for Molecular Life Sciences, University of Nijmegen, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
    Biochem J 360:421-9. 2001
    ..We conclude that the subcellular localization of p24 proteins is dynamic and depends on the biosynthetic activity of the cell...
  11. ncbi Cell-type-specific and selectively induced expression of members of the p24 family of putative cargo receptors
    Jutta Rötter
    Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences NCMLS, University of Nijmegen, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
    J Cell Sci 115:1049-58. 2002
    ....
  12. ncbi Effects of adrenalectomy on AGRP, POMC, NPY and CART gene expression in the basal hypothalamus of fed and fasted rats
    Eriika Savontaus
    Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Brain Res 958:130-8. 2002
    ..Furthermore, glucocorticoids are not required for fasting-induced upregulation of AGRP and NPY expression...
  13. pmc Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting
    Flavio S J de Souza
    INGEBI CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
    Mol Cell Biol 25:3076-86. 2005
    ..Our study advances the understanding of the molecular nature of hypothalamic POMC neurons and will be useful to determine whether polymorphisms in POMC regulatory regions play a role in the predisposition to obesity...
  14. ncbi Effects of leptin on arcuate pro-opiomelanocortin and cocaine-amphetamine-regulated transcript expression are independent of circulating levels of corticosterone
    N Vrang
    Rheoscience, Rødovre, Denmark
    J Neuroendocrinol 14:880-6. 2002
    ..The present data support the view that leptin influences arcuate POMC and CART mRNA expression directly, and that the effect is not modulated by corticosterone across a wide range of circulating corticosterone concentrations...
  15. ncbi Activation of central melanocortin pathways by fenfluramine
    Lora K Heisler
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Science 297:609-11. 2002
    ..These results provide a mechanistic explanation of d-FEN's anorexic actions and indicate that drugs targeting these downstream melanocortin pathways may prove to be effective and more selective anti-obesity treatments...
  16. ncbi Divergent regulation of proopiomelanocortin neurons by leptin in the nucleus of the solitary tract and in the arcuate hypothalamic nucleus
    Lihong Huo
    Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Diabetes 55:567-73. 2006
    ..We conclude that POMC neurons in the NTS do not respond to leptin unlike ARC POMC neurons. POMC neurons in the hypothalamus may therefore mediate all of leptin's signaling via POMC-derived peptides in the central nervous system...
  17. ncbi Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells
    Paul Kievit
    Division of Endocrinology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell Metab 4:123-32. 2006
    ..These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism...
  18. pmc PI3K integrates the action of insulin and leptin on hypothalamic neurons
    Allison Wanting Xu
    Department of Genetics, Stanford University School of Medicine, Stanford, California, USA
    J Clin Invest 115:951-8. 2005
    ..These results suggest a new view of hypothalamic circuitry, in which the effects of leptin and insulin are integrated by anorexigenic but not by orexigenic neurons...
  19. pmc Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity
    Leona Plum
    Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne and Center of Molecular Medicine Cologne CMMC, Cologne, Germany
    J Clin Invest 116:1886-901. 2006
    ..Moreover, icv administration of tolbutamide abolished hyperphagia in PPKO mice. These data indicate that PIP3-mediated signals are critical regulators of the melanocortin system via modulation of KATP channels...
  20. pmc Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice
    Jennifer W Hill
    Division of Hypothalamic Research, Department of Internal Medicine and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 118:1796-805. 2008
    ....
  21. ncbi Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions
    M L Raffin-Sanson
    Institut Cochin, Departement d Endocrinologie, Universite Rene Descartes Paris V, France
    Eur J Endocrinol 149:79-90. 2003
    ..A still unknown function in the placenta is likely.POMC has become a paradigmatic polypeptide precursor model illustrating the variable roles of a single gene and its various products in different localities...
  22. ncbi Serotonin 5-hydroxytryptamine2C receptor signaling in hypothalamic proopiomelanocortin neurons: role in energy homeostasis in females
    Jian Qiu
    Department of Physiology and Pharmacology, L334, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Mol Pharmacol 72:885-96. 2007
    ..Therefore, the Galpha(q) signaling pathways of the mER and 5-HT(2C) receptors may converge to enhance synaptic efficacy in brain circuits that are critical for maintaining homeostatic functions...
  23. pmc Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice
    Su Qian
    Department of Obesity and Metabolic Research, Merck Research Laboratories, Rahway, NJ 07065, USA
    Mol Cell Biol 22:5027-35. 2002
    ..Our results demonstrate that neither AgRP nor NPY is a critically required orexigenic factor, suggesting that other pathways capable of regulating energy homeostasis can compensate for the loss of both AgRP and NPY...
  24. ncbi Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels
    Nurhadi Ibrahim
    Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    Endocrinology 144:1331-40. 2003
    ..Therefore, it appears that POMC neurons may function as an integrator of metabolic cues and synaptic input for controlling homeostasis in the mammal...
  25. pmc AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons
    Marc Claret
    Centre for Diabetes and Endocrinology, Rayne Institute, University College London, London, United Kingdom
    J Clin Invest 117:2325-36. 2007
    ....
  26. ncbi The central melanocortin system and the integration of short- and long-term regulators of energy homeostasis
    Kate L J Ellacott
    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    Recent Prog Horm Res 59:395-408. 2004
    ....
  27. pmc Effects of hypothalamic neurodegeneration on energy balance
    Allison Wanting Xu
    Department of Genetics, Stanford University School of Medicine, Stanford, California, USA
    PLoS Biol 3:e415. 2005
    ..These findings provide new insight into the roles of hypothalamic neurons in energy balance regulation, and provide a model for understanding defects in human energy balance associated with neurodegeneration and aging...
  28. pmc Leptin-dependent control of glucose balance and locomotor activity by POMC neurons
    Lihong Huo
    Department of Medicine, Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 9:537-47. 2009
    ..Our results suggest that leptin signaling exclusively in POMC neurons is sufficient to stimulate locomotion and prevent diabetes in the severely hypoactive and hyperglycemic obese Lepr(db/db) mice...
  29. ncbi Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin
    L Yaswen
    Unit on Molecular Genetics, Clinical Neuroscience Branch, NIMH, 49 Convent Drive, Bethesda, Maryland 20892, USA
    Nat Med 5:1066-70. 1999
    ..Our results identify the POMC-null mutant mouse as a model for studying the human POMC-null syndrome, and indicate the therapeutic use of peripheral melanocortin in the treatment of obesity...
  30. ncbi Neuropeptide Y-mediated inhibition of proopiomelanocortin neurons in the arcuate nucleus shows enhanced desensitization in ob/ob mice
    Aaron G Roseberry
    Laboratory of Molecular Genetics, The Rockefeller University, 1230 York Avenue, Box 305, New York, NY 10021, USA
    Neuron 41:711-22. 2004
    ..These data reveal an intricate and asymmetric interplay between NPY and POMC neurons in the hypothalamus and have important implications for the delineation of the neural circuits that regulate feeding behavior...
  31. ncbi Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans
    H Krude
    Department of Pediatrics, Charite, Campus Virchow, Humboldt University Berlin, Germany
    Nat Genet 19:155-7. 1998
    ..These findings represent the first examples of a genetic defect within the POMC gene and define a new monogenic endocrine disorder resulting in early-onset obesity, adrenal insufficiency and red hair pigmentation...
  32. pmc Specific physiological roles for signal transducer and activator of transcription 3 in leptin receptor-expressing neurons
    Merisa L Piper
    Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA
    Mol Endocrinol 22:751-9. 2008
    ..These results further suggest that leptin's effects on growth and reproduction are mediated by other signaling pathways, and that Stat3-mediated control of these functions is mediated independently of leptin and LepRb neurons...
  33. ncbi Effects of leptin and corticosterone on the expression of corticotropin-releasing hormone, agouti-related protein, and proopiomelanocortin in the brain of ob/ob mouse
    K Arvaniti
    Centre de Recherche de l Hôpital Laval et Centre de Recherche sur le Métabolisme Energétique, Universite Laval, Quebec, Canada
    Neuroendocrinology 73:227-36. 2001
    ..Finally, the present results suggest that the effects of leptin on the expression of CRH, POMC and AGRP are not curbed by glucocorticoids...
  34. ncbi Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding
    Allison W Xu
    Department of Genetics, Stanford University School of Medicine, San Francisco, California 94143, USA
    Endocrinology 148:72-80. 2007
    ....
  35. doi PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response
    Bengt F Belgardt
    Institute for Genetics, Department of Mouse Genetics and Metabolism, Center for Molecular Medicine Cologne CMMC, University of Cologne, D 50674 Cologne, Germany
    Cell Metab 7:291-301. 2008
    ..These results reveal important but differential roles for PDK1 signaling in hypothalamic and pituitary POMC cells in the control of energy homeostasis and stress response...
  36. ncbi The melanocortin system in Fugu: determination of POMC/AGRP/MCR gene repertoire and synteny, as well as pharmacology and anatomical distribution of the MCRs
    Janis Klovins
    Department of Neuroscience, Uppsala University, Uppsala, Sweden
    Mol Biol Evol 21:563-79. 2004
    ....
  37. pmc Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways
    Ligang Zhou
    Department of Clinical Biochemistry, Addenbrooke s Hospital, University of Cambridge, Cambridge CB2 2QQ, UK
    Cell Metab 6:398-405. 2007
    ....
  38. pmc Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion
    Esther van de Wall
    Departments of Medicine and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 12461, USA
    Endocrinology 149:1773-85. 2008
    ....
  39. ncbi The catabolic action of insulin in the brain is mediated by melanocortins
    Stephen C Benoit
    Department of Psychiatry, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267 0559, USA
    J Neurosci 22:9048-52. 2002
    ..These data suggest that the hypothalamic melanocortin system mediates the anorexic effects of central insulin, as well as of leptin...
  40. ncbi Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production
    A Christine Könner
    Department of Mouse Genetics and Metabolism, Institute for Genetics, Center for Molecular Medicine, University of Cologne, D 50674 Cologne, Germany
    Cell Metab 5:438-49. 2007
    ..However, insulin action specifically in AgRP-expressing neurons does play a critical role in controlling hepatic glucose production and may provide a target for the treatment of insulin resistance in type 2 diabetes...
  41. ncbi Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain
    Shaaban A Mousa
    Klinik fur Anaesthesiologie und operative Intensivmedizin, Charite Universitatsmedizin Berlin, Campus Benjamin Franklin, D 12200 Berlin, Germany
    Endocrinology 145:1331-41. 2004
    ..Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules...
  42. pmc Expression of two proopiomelanocortin genes in the pituitary gland of Xenopus laevis: complete structures of the two preprohormones
    G J Martens
    Nucleic Acids Res 14:3791-8. 1986
    ....
  43. ncbi Subfunctionalization of expression and peptide domains following the ancient duplication of the proopiomelanocortin gene in teleost fishes
    Flavio S J de Souza
    Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular, CONICET, FCEyN, Universidad de Buenos Aires, Argentina
    Mol Biol Evol 22:2417-27. 2005
    ..The study of regulatory regions of fish POMC genes might shed light on the mechanisms of enhancer partitioning between duplicate genes, as well as the roles of POMC-derived peptides in fish physiology...
  44. ncbi Agouti-related peptide-expressing neurons are mandatory for feeding
    Eva Gropp
    Institute for Genetics and Center for Molecular Medicine CMMC, Department of Mouse Genetics and Metabolism, University of Cologne, Zülpicher Str 47, 50674 Koln, Germany
    Nat Neurosci 8:1289-91. 2005
    ....
  45. doi Hyperphagia and increased meal size are responsible for weight gain in rats treated sub-chronically with olanzapine
    Nima Davoodi
    Department of Psychology, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK
    Psychopharmacology (Berl) 203:693-702. 2009
    ..Atypical antipsychotic-induced weight gain is a significant impediment in the treatment of schizophrenia...
  46. ncbi Neuropeptide processing and its impact on melanocortin pathways
    Lynn E Pritchard
    Endocrine Sciences, University of Manchester, UCTF Building, 46 Grafton Street, Manchester M13 9NT, United Kingdom
    Endocrinology 148:4201-7. 2007
    ..Overall, these studies implicate POMC processing as a key regulatory mechanism in the control of energy homeostasis...
  47. ncbi The melanocortin system
    Ira Gantz
    Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109 0682, USA
    Am J Physiol Endocrinol Metab 284:E468-74. 2003
    ..Development of selective agonists and antagonists is expected to further facilitate the investigation of these complex physiological functions and provide an experimental basis for new pharmacotherapies...
  48. ncbi CRF and stress in fish
    Gert Flik
    Department of Animal Physiology, Institute for Neuroscience, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands
    Gen Comp Endocrinol 146:36-44. 2006
    ..Understanding of stress during early life stages is critical as the consequent rises in cortisol may have long lasting effects on survival and fish quality...
  49. ncbi Characterization of glucosensing neuron subpopulations in the arcuate nucleus: integration in neuropeptide Y and pro-opio melanocortin networks?
    Xavier Fioramonti
    Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5018, Paul Sabatier University, Toulouse, France
    Diabetes 56:1219-27. 2007
    ..Taken together, hypo- and hyperglycemia are detected by distinct populations of glucosensing neurons, and POMC and NPY neurons are not solely responsible for ARC glucosensing...
  50. ncbi Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats
    P J Havel
    Department of Nutrition, University of California, Davis 95616, USA
    Diabetes 49:244-52. 2000
    ..These responses, in concert with increased muscle UCP-3 expression, may also contribute to the catabolic effects of uncontrolled diabetes on fuel metabolism in peripheral tissues...
  51. pmc The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake
    Leona Plum
    Naomi Berrie Diabetes Center and Department of Medicine, Columbia University, New York, New York, USA
    Nat Med 15:1195-201. 2009
    ..The dissociation of food intake from energy expenditure in Pomc-Foxo1(-/-) mice represents a model for therapeutic intervention in obesity and raises the possibility of targeting Cpe to develop weight loss medications...
  52. ncbi Impaired prohormone convertases in Cpe(fat)/Cpe(fat) mice
    Y Berman
    Department of Pharmacology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA
    J Biol Chem 276:1466-73. 2001
    ....
  53. ncbi Characterization of a serine protease that cleaves pro-gamma-melanotropin at the adrenal to stimulate growth
    A B Bicknell
    School of Animal and Microbial Sciences, The University of Reading, Whiteknights, PO Box 228, Reading, Berkshire, RG6 6AJ, United Kingdom
    Cell 105:903-12. 2001
    ..We also show that it is required for growth of Y1 cells, remains bound to the cell surface, and cleaves its substrate, pro-gamma-MSH, at a specific bond...
  54. ncbi Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity
    Laura E Parton
    Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nature 449:228-32. 2007
    ..We conclude that obesity-induced, UCP2-mediated loss of glucose sensing in glucose-excited neurons might have a pathogenic role in the development of type 2 diabetes...
  55. ncbi The effects of proopiomelanocortin deficiency on murine adrenal development and responsiveness to adrenocorticotropin
    Anthony P Coll
    Department of Medicine, Box 232, Addenbrooke s Hospital, Cambridge CB2 2QR, United Kingdom
    Endocrinology 145:4721-7. 2004
    ..Although such glands are atrophic and hypofunctional, exposure to ACTH alone can restore their size, morphology, and corticosterone secretion...
  56. ncbi Ontogenic expression of putative feeding peptides in the rat fetal brain and placenta
    R Beloosesky
    Department of Obstetrics and Gynecology, Harbor UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, USA
    Nutr Neurosci 9:33-40. 2006
    ..The continued maturation of feeding regulatory mechanisms in late gestation indicates the potential for in utero programming of ingestive behavior...
  57. ncbi Differential effects of fasting and leptin on proopiomelanocortin peptides in the arcuate nucleus and in the nucleus of the solitary tract
    Mario Perello
    Division of Endocrinology, Department of Medicine, Brown University, Rhode Island Hospital, Providence, Rhode Island 02903, USA
    Am J Physiol Endocrinol Metab 292:E1348-57. 2007
    ..This represents a novel aspect in the regulation of energy balance and may have implications in the pathophysiology of obesity...
  58. ncbi Gene therapy for bladder pain with gene gun particle encoding pro-opiomelanocortin cDNA
    Yao Chi Chuang
    Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China
    J Urol 170:2044-8. 2003
    ..In this study we developed a gene gun method for the transfer of POMC cDNA in vivo and investigated its therapeutic effect on acetic acid induced bladder hyperactivity in rats...
  59. ncbi Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin
    Fang Cai
    Department of Physiology, University of Toronto, Medical Sciences Building 3247A, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    J Endocrinol 192:605-14. 2007
    ....
  60. ncbi Brain stem melanocortinergic modulation of meal size and identification of hypothalamic POMC projections
    Huiyuan Zheng
    Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Rd, Baton Rouge, LA 70808, USA
    Am J Physiol Regul Integr Comp Physiol 289:R247-58. 2005
    ....
  61. ncbi Electroporation-mediated pain-killer gene therapy for mononeuropathic rats
    C R Lin
    Department of Biological Sciences, National Sun Yat Sen University, Taiwan
    Gene Ther 9:1247-53. 2002
    ..This result suggests that gene therapy for neuropathic pain using this novel technique is very efficacious, and thus shows promise for further clinical trials...
  62. doi Functional diversity among p24 subfamily members
    Jeroen R P M Strating
    Department of Molecular Animal Physiology, Donders Centre for Neuroscience and Nijmegen Centre for Molecular Life Sciences NCMLS, Faculty of Science, Radboud University, 6525 GA Nijmegen, The Netherlands
    Biol Cell 101:207-19. 2009
    ....
  63. ncbi Transgene-driven protein expression specific to the intermediate pituitary melanotrope cells of Xenopus laevis
    Eric J R Jansen
    Department of Molecular Animal Physiology, Nijmegen Centre for Molecular Life Sciences, University of Nijmegen, Geert Grooteplein Zuid 28, 6525GA, Nijmegen, The Netherlands
    FEBS Lett 516:201-7. 2002
    ..Hence, stable Xenopus transgenesis with the POMC gene promoter is a powerful tool to study the physiological role of proteins in a well-defined neuroendocrine system and close to the in vivo situation...
  64. pmc Disparate effects of p24alpha and p24delta on secretory protein transport and processing
    Jeroen R P M Strating
    Department of Molecular Animal Physiology, Nijmegen Centre for Molecular Life Sciences, Institute for Neuroscience, Faculty of Science, Radboud University, Nijmegen, The Netherlands
    PLoS ONE 2:e704. 2007
    ....
  65. ncbi Isolation and structure-bioactivity characterization of glycosylated N-pro-opiomelanocortin isoforms
    J Lu
    Laboratory of Cell Pharmacology, University of Leuven KU Leuven, Medical School, Gasthuisberg O and N, Belgium
    J Neuroendocrinol 14:869-79. 2002
    ..The data also show the essential role of N-glycosylation in the biological response...
  66. ncbi Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats
    B E Levin
    Neurology Service, Department of Veterans Affairs New Jersey Health Care System, East Orange 07018, USA
    Am J Physiol Regul Integr Comp Physiol 279:R2222-8. 2000
    ..Thus sibutramine lowered the defended body weight in association with compensatory changes in those central pathways involved in energy homeostasis...
  67. ncbi Lymphocytes upregulate signal sequence-encoding proopiomelanocortin mRNA and beta-endorphin during painful inflammation in vivo
    Nicolle Sitte
    Department of Anesthesiology and Critical Care Medicine, Charite University Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
    J Neuroimmunol 183:133-45. 2007
    ..Semi-nested PCR revealed 8-fold increased exon 2-3 spanning POMC mRNA. Thus, painful inflammation enhances signal sequence-encoding lymphocytic POMC mRNA needed for regulated secretion of functionally active END...
  68. ncbi Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons
    Pablo J Enriori
    Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA
    Cell Metab 5:181-94. 2007
    ..These results highlight the physiological importance of leptin sensing in the melanocortin circuits and show that their loss of leptin sensing likely contributes to the pathology of leptin resistance...
  69. pmc Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36)
    B G Challis
    Department of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge CB2 2XY, United Kingdom
    Proc Natl Acad Sci U S A 101:4695-700. 2004
    ....
  70. ncbi Gut hormone PYY(3-36) physiologically inhibits food intake
    Rachel L Batterham
    Imperial College Faculty of Medicine at Hammersmith Campus, Du Cane Road, London W12 0NN, UK
    Nature 418:650-4. 2002
    ..Thus, postprandial elevation of PYY(3-36) may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway...
  71. ncbi Is the energy homeostasis system inherently biased toward weight gain?
    Michael W Schwartz
    Department of Medicine, University of Washington, Seattle, USA
    Diabetes 52:232-8. 2003
    ..Teleological, molecular, physiological, and clinical aspects of this hypothesis are presented, along with a discussion of currently available supporting evidence...
  72. pmc Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors
    Daniel D Lam
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom
    Endocrinology 149:1323-8. 2008
    ..X warrants further investigation as a treatment for obesity but also elucidate specific neuronal pathways potently affecting energy balance through which 5-HT(2C)R agonists regulate ingestive behavior...
  73. ncbi Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake
    Tadahiro Kitamura
    Department of Medicine, Columbia University Medical Center, 1150 St Nicholas Avenue, New York, New York 10032, USA
    Nat Med 12:534-40. 2006
    ..Thus, FoxO1 represents a shared component of pathways integrating food intake and peripheral metabolism...
  74. ncbi Hypothalamic, metabolic, and behavioral responses to pharmacological inhibition of CNS melanocortin signaling in rats
    T Adage
    Department of Animal Physiology, University of Groningen, 9750 AA Haren, The Netherlands
    J Neurosci 21:3639-45. 2001
    ..e., CART, POMC, and NPY) and paraventricular (i.e., CRH) hypothalamus. The results indicate that reduced activity of the CNS MC pathway promotes fat deposition via both food intake-dependent and -independent mechanisms...
  75. ncbi In vivo electroporation of proopiomelanocortin induces analgesia in a formalin-injection pain model in rats
    Tsung Hsing Lee
    Anesthesiology Research Laboratory, Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Tao Yuan, Taiwan, ROC
    Pain 104:159-67. 2003
    ..We conclude that electroporation successfully delivered intrathecally administered pCMV-hPOMC into the dorsal horn cells of the spinal cord, and induced analgesia in phase 2 of the formalin test in rats...
  76. ncbi Regulation of prohormone convertases in hypothalamic neurons: implications for prothyrotropin-releasing hormone and proopiomelanocortin
    Eduardo A Nillni
    Division of Endocrinology, Department of Medicine, Brown Medical School Rhode Island Hospital, 55 Claverick Street, Third Floor, Room 320, Providence, Rhode Island 02903, USA
    Endocrinology 148:4191-200. 2007
    ..Therefore, the coupled regulation of proneuropeptide/processing enzymes may be a common process, by which cells generate more effective processing of prohormones into mature peptides...
  77. ncbi The central melanocortin system regulates food intake in goldfish
    Jose Miguel Cerdá-Reverter
    Department of Biological Sciences, University of Alberta, T6G 2E9, Edmonton, Alberta, Canada
    Regul Pept 115:101-13. 2003
    ..The conserved central expression pattern of POMC mRNA and role of MSH peptides in physiological regulation of food intake suggests that melanocortin functions were gained early in vertebrate evolution...
  78. pmc Differential induction of two p24delta putative cargo receptors upon activation of a prohormone-producing cell
    R P Kuiper
    Department of Animal Physiology, University of Nijmegen, Nijmegen, The Netherlands
    Mol Biol Cell 11:131-40. 2000
    ..Therefore, the expression of Xp24delta(2) specifically correlates with the expression of POMC. Together, our findings suggest that p24delta proteins have a role in selective protein transport in the secretory pathway...
  79. ncbi Acute effects of PYY3-36 on food intake and hypothalamic neuropeptide expression in the mouse
    B G Challis
    Department of Medicine and Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, CB2 2QQ, Cambridge, UK
    Biochem Biophys Res Commun 311:915-9. 2003
    ..This is associated with a short-lived suppression of NPY mRNA, a longer lasting increase in POMC mRNA but no change in MCH mRNA expression...
  80. ncbi Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system
    Wei Fan
    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    Nat Neurosci 7:335-6. 2004
    ....
  81. ncbi Peptide YY3-36 inhibits food intake in mice through a melanocortin-4 receptor-independent mechanism
    Ilia G Halatchev
    Ph D, Vollum Institute, Center for the Study of Weight Regulation and Associated Disorders, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239 3098, USA
    Endocrinology 145:2585-90. 2004
    ..Thus, unlike cholecystokinin, PYY(3-36)-induced satiety is atypical, because it does not produce detectable activation of brainstem satiety centers and is not dependent on MC4-R signaling...
  82. ncbi Resistance to diet-induced obesity is associated with increased proopiomelanocortin mRNA and decreased neuropeptide Y mRNA in the hypothalamus
    H T Bergen
    Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada
    Brain Res 851:198-203. 1999
    ....
  83. ncbi The melanocortin system as a central integrator of direct and indirect controls of food intake
    Diana L Williams
    Am J Physiol Regul Integr Comp Physiol 289:R2-3. 2005
  84. ncbi 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway
    J A Braks
    Department of Animal Physiology, University of Nijmegen, The Netherlands
    Cell 78:263-73. 1994
    ..Our results suggest that 7B2 is a novel type of molecular chaperone preventing premature activation of proPC2 in the regulated secretory pathway...
  85. ncbi Lack of proopiomelanocortin peptides results in obesity and defective adrenal function but normal melanocyte pigmentation in the murine C57BL/6 genetic background
    James L Smart
    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    Ann N Y Acad Sci 994:202-10. 2003
    ....
  86. ncbi Post-translational modification of bovine pro-opiomelanocortin. Tyrosine sulfation and pyroglutamate formation, a mass spectrometric study
    A Bateman
    Endocrine Laboratory, Royal Victoria Hospital, Montreal, Quebec, Canada
    J Biol Chem 265:22130-6. 1990
    ..This reaction is thought to be catalyzed by a pyroglutamate forming enzyme located within the secretory granule fraction. Under certain circumstances peptides with glutamate at their amino termini may act as substrates for this enzyme...
  87. ncbi Altered processing of pro-orphanin FQ/nociceptin and pro-opiomelanocortin-derived peptides in the brains of mice expressing defective prohormone convertase 2
    R G Allen
    Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    J Neurosci 21:5864-70. 2001
    ..These results demonstrate that PC2 is directly involved in the biogenesis of two brain neuropeptides in vivo and suggest that the specific prohormone and cellular context influences neuropeptide processing by PCs...
  88. ncbi Trends in the evolution of the proopiomelanocortin gene
    Robert M Dores
    University of Denver, Department of Biological Sciences, Denver, CO 80208, USA
    Gen Comp Endocrinol 142:81-93. 2005
    ....
  89. ncbi The proopiomelanocortin system
    M E Hadley
    Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson 85724 5044, USA
    Ann N Y Acad Sci 885:1-21. 1999
    ..For example, melanocortin-induced satiety can be antagonized by a melanocortin antagonist. Defects in melanocortin ligand biosynthesis, secretion, and melanocortin receptor function can lead to a diverse number of pathological states...
  90. ncbi Obliteration of alpha-melanocyte-stimulating hormone derived from POMC in pituitary and brains of PC2-deficient mice
    Ruthellen Miller
    Buck Institute for Age Research, Novato, California 94945, USA
    J Neurochem 86:556-63. 2003
    ..Overall, these studies demonstrated that the PC2 processing enzyme is critical for the in vivo production of alpha-MSH in pituitary and brain...
  91. pmc A cell-specific transgenic approach in Xenopus reveals the importance of a functional p24 system for a secretory cell
    Gerrit Bouw
    Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences, University of Nijmegen, 6525 GA Nijmegen, The Netherlands
    Mol Biol Cell 15:1244-53. 2004
    ....
  92. ncbi Proopiomelanocortin-deficient mice are hypersensitive to the adverse metabolic effects of glucocorticoids
    Anthony P Coll
    University Department of Medicine, Addenbrooke s Hospital, Cambridge CB2 2QR, UK
    Diabetes 54:2269-76. 2005
    ..This may occur through a mechanism involving the suppression of AgRP by the hypoadrenal state...
  93. ncbi Agouti-related protein (AGRP) is conserved and regulated by metabolic state in the zebrafish, Danio rerio
    Youngsup Song
    Vollum Institute, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Endocrine 22:257-65. 2003
    ....
  94. ncbi Regulated, electroporation-mediated delivery of pro-opiomelanocortin gene suppresses chronic constriction injury-induced neuropathic pain in rats
    C M Wu
    Department of Biological Sciences, National Sun Yat Sen University, Taiwan
    Gene Ther 11:933-40. 2004
    ..We concluded that intrathecal pTRE2-POMC/pTel-off electroporation alleviates CCI-induced limb pain, and can be controlled by intraperitoneal doxycycline administration...
  95. pmc The role of insulin receptor substrate 2 in hypothalamic and beta cell function
    Agharul I Choudhury
    Centre for Diabetes and Endocrinology, Rayne Institute, University College London, London, United Kingdom
    J Clin Invest 115:940-50. 2005
    ..Our findings demonstrate a critical role for IRS2 in beta cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis...
  96. ncbi Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity
    M Rios
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Mol Endocrinol 15:1748-57. 2001
    ..Our results demonstrate that brain derived neurotrophic factor has an essential maintenance function in the regulation of anxiety-related behavior and in food intake through central mediators in both the basal and fasted state...
  97. ncbi Various dietary fats differentially change the gene expression of neuropeptides involved in body weight regulation in rats
    B Dziedzic
    Department of Cell to Cell Communication, Medical University of Lodz, Lodz, Poland
    J Neuroendocrinol 19:364-73. 2007
    ..The present study demonstrates that various forms of dietary fat differentially change the expression of neuropeptide genes involved in energy homeostasis...
  98. doi Effects of fluoxetine administration on hypothalamic melanocortin system in obese Zucker rats
    I Churruca
    Department of Nutrition and Food Science, University of the Basque Country, Paseo de la Universidad 7, Vitoria, Spain
    Neuropeptides 42:293-9. 2008
    ..These results suggest the involvement of alpha-MSH in central fluoxetine anorectic action...
  99. ncbi Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis
    Joel K Elmquist
    Department of Medicine and Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Comp Neurol 493:63-71. 2005
    ..Finally, although these studies have been illustrative, they also underscore our relative lack of knowledge and highlight the need for more definitive approaches to unravel the functional significance of these pathways...
  100. ncbi Obesity-prone rats have preexisting defects in their counterregulatory response to insulin-induced hypoglycemia
    Nancy C Tkacs
    University of Pennsylvania School of Nursing, Philadelphia 19104 6096, USA
    Am J Physiol Regul Integr Comp Physiol 287:R1110-5. 2004
    ..These data suggest that DIO rats have a preexisting defect in their CRR to IIH but that IIH does not affect the expression of their hypothalamic neuropeptides or weight gain as it does in DR rats...
  101. ncbi Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptor-deficient mice
    Janine Arens
    Dr Senckenbergische Anatomie, Institut fuer Anatomie II, Fachbereich Medizin, Johann Wolfgang Goethe Universitaet, D 60590 Frankfurt Main
    Physiol Genomics 16:38-46. 2003
    ..Negative feedback control by body fat content on ARC neuropeptide expression is present in young animals but vanishes with age and is modulated by MC4R deficiency...

Research Grants67

  1. Central Action of Brain-Derived Neurotrophic Factor in Male and Female Rats
    Haifei Shi; Fiscal Year: 2010
    ....
  2. Arcuate nucleus glutamatergic neurons modulate energy homeostasis
    Anthony N van den Pol; Fiscal Year: 2013
    ..abstract_text> ..
  3. Role of beta-endorphin in cancer therapy induced fatigue
    David E Fisher; Fiscal Year: 2013
    ..This 2-endorphin - fatigue axis offers a profound treatment opportunity to improve quality of life in cancer patients, which we will examine in a human clinical trial and a series of preclinical animal studies. ..
  4. Simultaneous Insulin and Leptin Signaling in POMC Neurons Promotes Fertility and
    LATRICE DOREEN FAULKNER; Fiscal Year: 2013
    ..Collectively, these experiments will establish whether the absence of insulin and leptin signaling in POMC neurons elevates LH pulse secretion and testosterone release, thus impairing the steroidal negative feedback. ..
  5. Humoral factors in gender differences in blood pressure control
    Jane F Reckelhoff; Fiscal Year: 2013
    ..Results from these studies will provide new information that can be used to design new therapeutic options to treat HT in women with hyperandrogenemia, such as in PCOS. ..
  6. Sex Differences in the Cannabioid Regulation of Energy Homeostasis
    Edward J Wagner; Fiscal Year: 2013
    ....
  7. Systemic Factors that Maintain a Young Liver Phenotype
    Roy G Smith; Fiscal Year: 2012
    ..Ghrelin levels decline as a function of age. Our research is designed to test whether replacing this hormone with a more stable form will provide health and quality of life benefits during aging. ..
  8. Interaction of Estrogen and AMPK in the Hypothalamus
    Jessica Healy; Fiscal Year: 2012
    ..The proposed project will investigate the cellular mechanisms underlying the interaction between food intake and reproductive hormones, and the results may be useful in mitigating the pathological effects of certain types of obesity. ..
  9. Neurochemistry/physiology of proopiomelanocortin neurons
    MALCOLM JAMES LOW; Fiscal Year: 2013
    ....
  10. BRAIN GLUCOSENSING NEURONS IN HEALTH AND DIABETES
    Barry E Levin; Fiscal Year: 2013
    ....
  11. Cathepsin L in the Biosynthesis of Enkephalins and beta-Endorphin Opioid Peptides
    Steven J Bark; Fiscal Year: 2012
    ....
  12. Hypothalamic autophagy and metabolic regulation in aging
    Rajat Singh; Fiscal Year: 2013
    ....
  13. INTERACTIONS OF LEPTIN AND CENTRAL SEROTONIN SYSTEMS
    Joel K Elmquist; Fiscal Year: 2013
    ..Results from these studies will advance our understanding of the serotoninergic circuits necessary to permit the design of effective treatment strategies for obesity and diabetes. ..
  14. Inflammatory Cytokine regulation of POMC and Orexin neurons in cachexia.
    AARON GROSSBERG; Fiscal Year: 2012
    ..This research is designed to understand how disease causes these devastating reductions in eating and activity level as a means to develop new therapies. ..
  15. Proopiomelanocortin gene expression and obesity
    MALCOLM JAMES LOW; Fiscal Year: 2013
    ....
  16. Phosphodiesterase-3B signaling in the Hypothalamus and Obesity
    Abhiram Sahu; Fiscal Year: 2013
    ..Overall, these studies will define the critical role of PDE3B signaling in the hypothalamus in the context of the physiology and pathophysiology of energy homeostasis. ..
  17. BETA ENDORPHIN NEURONS AND THE CONTROL OF HOMEOSTASIS
    MARTIN JEFFREY KELLY; Fiscal Year: 2013
    ....
  18. BETA ENDORPHIN NEURONS AND THE CONTROL OF HOMEOSTASIS
    Martin Kelly; Fiscal Year: 2009
    ..abstract_text> ..
  19. 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. ..
  20. STRESS-INDUCED ACTIVATION OF COLONIC MOTOR FUNCTION
    YVETTE FRANCE TACHE; Fiscal Year: 2013
    ....
  21. Hypothalamic Mechanisms in Cachexia
    Daniel L Marks; Fiscal Year: 2013
    ..Our data argues strongly that the hypothalamic melanocortin system plays a critical role in the transduction of illness-induced cachexia and therefore represents an important target for future therapeutic intervention. ..
  22. Physiological Role of CNS GLP-2 Receptor in Energy Homeostasis
    Xinfu Guan; Fiscal Year: 2010
    ....
  23. AgRP neurons regulate bone remodeling in aging
    KARL LEONARD INSOGNA; Fiscal Year: 2013
    ..2008), we also predict that increasing ROS exposure of the melanocortin system during aging is a critical contributor to aging-associated bone loss and the pathogenesis of osteoporosis. ..
  24. CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETION
    Richard E Mains; Fiscal Year: 2013
    ....
  25. Altering Energy Balance by Systemic Delivery of RNAi to the Neuroendocrine Brain
    Sergio R Ojeda; Fiscal Year: 2013
    ..We also anticipate that these studies will provide the basis for new delivery strategies to the brain for basic research purposes and emerging therapies. ..
  26. Melanocortin Neuropeptides &Ethanol Intake
    Todd E Thiele; Fiscal Year: 2013
    ..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. ..
  27. A carboxypeptidase in the regulation of hypothalamic circuitry
    Sabrina Diano; Fiscal Year: 2013
    ..Successful completion of these studies will deliver new drug targets for metabolic disorders, including obesity and type 2 diabetes. ..
  28. Role of Peroxisome Proliferation in Leptin Resistance
    Sabrina Diano; Fiscal Year: 2013
    ....
  29. CSF Neuropeptide, Hormonal and Metabolomic Analysis in Human Energy Balance
    Sharon L Wardlaw; Fiscal Year: 2013
    ..An important goal is to identify biomarkers in CSF that could predict responses to dieting and to pharmacotherapy for obesity that target the melanocortin system. ..
  30. Diet-Induced Plasticity of Proopiomelanocortin Neurons
    AARON JEFFREY MERCER; Fiscal Year: 2012
    ....
  31. Hypothalamic GABAergic Action and Energy Homeostasis
    Qingchun Tong; Fiscal Year: 2010
    ..abstract_text> ..
  32. Cross-talk between Leptin and Estrogen Signaling in Hypothalamic Arcuate Neurons
    Oline K Ronnekleiv; Fiscal Year: 2013
    ..Understanding the convergence of leptin and E2 signaling in arcuate kisspeptin neurons will provide insight into the fundamental role of these hormones in conveying metabolic cues to the reproductive axis. ..
  33. Energy Homeostasis: GABAergic and Non-GABAergic POMC Neurons
    Young Hwan Jo; Fiscal Year: 2013
    ..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. ..
  34. Role of Endogenous Opiate Systems in Cocaine Relapse after Long-Term Abstinence
    David W Self; Fiscal Year: 2013
    ..Together, these studies will determine the role of persistent neuroadaptations in endogenous mu opiate receptor systems in the increased propensity for cocaine relapse in prolonged abstinence. ..
  35. Regulation of Energy Homeostasis by BDNF
    Baoji Xu; Fiscal Year: 2013
    ..Findings from this proposed project would provide insights into the mechanism by which BDNF regulates energy balance as well as the role of structural changes in hypothalamic neural circuits in the development of obesity. ..
  36. 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. ..
  37. The Central Melanocortin System and Regulation of Energy Balance
    Sharon L Wardlaw; Fiscal Year: 2012
    ....
  38. Leptin and Insulin Responses in Hypothalamic NPY Neurons
    CHRISTOPHER JAVADI; Fiscal Year: 2013
    ..Determining these pathways may reveal insights into how resistance to these signals occurs in obesity and type 2 diabetes. ..
  39. Developing tools for understanding neuromodulation of hypothalamic func
    Su Guo; Fiscal Year: 2013
    ..Equally importantly, this proposal will establish broadly applicable tools for genetically dissecting neuromodulatory systems in complex behaviors. ..
  40. OPIOID PEPTIDE SYNTHESIZING ENZYMES
    Iris Lindberg; Fiscal Year: 2013
    ..We are also interested in describing the molecular forms of a new peptide precursor we have observed in brain tissue. ..
  41. Defensins as Melanocortin Ligands
    Carrie Haskell-Luevano; Fiscal Year: 2013
    ..This proposal seeks to clarify this novel endogenous melanocortin receptor ligand family, gain fundamental knowledge, and develop molecular probes to use to determine their potential involvement with obesity and Type 2 diabetes. ..
  42. Localized Vulvodynia Pathogenesis: Fibroblast, Yeast, and Melanocortin
    Richard P Phipps; Fiscal Year: 2013
    ..We will assess an anti-inflammatory melanocortin derivative with therapeutic potential for vulvodynia and investigate the underlying molecular mechanism(s). ..
  43. Requirement of 5-HT2CRs in POMC and SIM1 neurons to Regulate Energy Homeostasis
    Eric Berglund; Fiscal Year: 2012
    ..These findings would improve our understanding about how the body controls energy homeostasis and potentially offer new therapeutic targets. ..
  44. Hypothalmic Circuits Regulating Energy Balance and Obesity: Synaptic Physiology
    SHANE THERESE HENTGES; Fiscal Year: 2013
    ..It may be that amino acid transmitters in feeding circuits will prove to be viable targets for manipulating energy balance regulation. ..
  45. OPIOMELANOCORTIN PEPTIDES AND CARDIOVASCULAR REGULATION
    George Kunos; Fiscal Year: 1999
    ..The results will help our understanding of anti hypertensive drug action, and will clarify the mechanism of cardiovascular regulation by POMC peptides. ..
  46. Role of CRH in skin physiology and pathology
    Andrzej Slominski; Fiscal Year: 2004
    ..g., melanocytes and keratinocytes, and test the role of CRH/CRH-R1 axis in the regulation of human hair growth. ..
  47. TUMOR CELL SYNTHESIS AND SECRETION OF PEPTIDE HORMONES
    David Orth; Fiscal Year: 1991
    ..The results of these studies will provide new insights into the phenomenon of peptide hormone synthesis and secretion by tumor cells...
  48. HYPOTHALAMIC CONTROL OF FEEDING AND METABOLISM
    ROGER CONE; Fiscal Year: 2003
    ..Finally, the specific hypothesis that altered levels of POMC gene expression may be a risk factor for obesity will be directly tested by Dr. Boston and his collaborators (project II). ..
  49. Opioid regulation of hypothalamic neurons
    SHANE THERESE HENTGES; Fiscal Year: 2013
    ....
  50. INTERLEUKIN REGULATION OF PROOPIOMELANOCORTIN GENE
    S Brown; Fiscal Year: 1990
    ..Finally, we will determine if like CRF, monokines and lymphokines stimulate cAMP generation in pituitary cells. These studies will determine if molecules of divergent origin produce common effects through similar mechanisms...
  51. REGULATION OF SECRETION OF POMC PEPTIDES IN BRAIN
    LEONARD KAPCALA; Fiscal Year: 1991
    ....
  52. Hypothalamic Regulation of Energy Homeostasis
    Sharon Wardlaw; Fiscal Year: 2004
    ..Our proposed studies of P0MG regulation and processing in the rodent should thus have implications for the regulation of food intake and body weight in the human. ..
  53. Neural-Specific Regulation of POMC Gene Expression
    Malcolm Low; Fiscal Year: 2005
    ....
  54. PRO-OPIOMELANOCORTIN SYNTHESIS IN TESTES
    Nathaniel Mills; Fiscal Year: 1992
    ..Regulation of POMC synthesis in the gonad may be very important and may provide insights for overall control of spermatogenesis...
  55. PITUITARY KALLIKREIN & PROHORMONE PROCESSING
    CLAUD POWERS; Fiscal Year: 1992
    ....
  56. gamma-MSH and Sodium Metabolism
    Michael Humphreys; Fiscal Year: 2007
    ....
  57. Role of Pro-opiomelanocortin mutations in human obesity
    Christian Vaisse; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  58. Epigenetics of alcohol effects on stress axis development
    DIPAK SARKAR; Fiscal Year: 2009
    ....
  59. POMC PROCESSING & BETA-ENDORPHIN RELATED OPIOID PEPTIDE
    Vivian Hook; Fiscal Year: 2000
    ..These studies will provide a comprehensive evaluation of primary POMC processing enzyme(s). ..
  60. HYPOGLYCEMIA-ASSOCIATED AUTONOMIC FAILURE AND THE BRAIN
    Nancy Tkacs; Fiscal Year: 2003
    ..The research plan, candidate, and environment are well-suited for an ongoing career in fundamental diabetes research. ..
  61. REGULATION OF ANTERIOR PITUITARY FUNCTION BY POMC
    Sharon Wardlaw; Fiscal Year: 1990
    ....
  62. OPIOID REGULATION OF POMC IN THE HYPOTHALAMUS
    Sharon Wardlaw; Fiscal Year: 2000
    ....
  63. Serotonin Mediated Responses to Energy Depletion
    Michael H Donovan; Fiscal Year: 2012
    ..Taken together, these experiments should increase the understanding of the complex regulation of energy balance by serotonin. ..
  64. STRUCTURAL DETERMINANTS IN REGULATION OF POMC PROCESSING
    Theodore Friedman; Fiscal Year: 1999
    ..These studies will provide valuable information on the subcellular mechanisms subserving the post- translational generation of beta-endorphin and related peptides. Thus, the biological basis for addiction may begin to be elucidated. ..
  65. PHYSIOLOGY OF PITUITARY CELL GLUCOCORTICOID BINDING
    Robert Harrison; Fiscal Year: 1993
    ....
  66. Discovery of Alpha-MSH Analogs for Skin Cancer Prevention
    Zalfa Abdel Malek; Fiscal Year: 2009
    ..abstract_text> ..
  67. Molecular Genetics of the HPA(I) Axis
    Phillip Danielson; Fiscal Year: 2002
    ....