title: Ingestion-controlling network: what's language got to do with it?
abstract: The prevalence of obesity has increased dramatically worldwide, whereas the types of treatment and their efficacy have not substantially changed over the last two decades. Additionally, drugs used to control weight gain could occasionally create untoward effects in cardiovascular functions, as well as in behaviors, memory, sleep, and emotions because the molecular machinery responsible for ingestion control is interconnected with or shared by the above domains. How each group of drugs preserves the privacy of its message in the mutual network is not fully understood. In the present essay, the graph theory approach was used to explore some aspects of molecular signaling as though they were a 'language'. Its emphasis is on 'molecular polysemy', a term that refers to the ability of biomolecules to be used like words in natural languages more than one-way. This has physiological and clinical implications, in particular when planning drug designs with "specially engineered shotgun loads" that target a combination of biomolecules that assure a better therapeutic outcome without causing deficits in connected but patho-physiologically irrelevant bystanders.
authors.affiliation: Clinical Brain Disorders Branch, NIMH/National Institutes of Health, Bethesda, MD 20892-1379, USA. myslobom@mail.nih.gov
authors.forename: Michael
authors.initials: M
authors.lastname: Myslobodsky
authors.forename: Richard
authors.initials: R
authors.lastname: Coppola
mesh_terms: D000818:Animals; D004435:Eating / Q000502:physiology*; D006801:Humans; D007802:Language; D008954:Models, Biological; D010455:Peptides / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D010455:Peptides
references.citation: Obes Facts. 2009;2(6):374-82
references.pmid: 20090389
references.citation: Front Biosci. 2008 Jan 01;13:2391-9
references.pmid: 17981720
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2005 Apr;71(4 Pt 2):046117
references.pmid: 15903736
references.citation: Neuroendocrinology. 1999 Sep;70(3):207-12
references.pmid: 10516484
references.citation: Obes Facts. 2008;1(2):93-102
references.pmid: 20054168
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9517-20
references.pmid: 11504940
references.citation: Fractals. 1995 Jun;3(2):269-84
references.pmid: 11539281
references.citation: Drug Discov Today. 2008 Jan;13(1-2):23-9
references.pmid: 18190860
references.citation: Nat Chem Biol. 2009 Mar;5(3):131-4
references.pmid: 19219011
references.citation: Biochem Soc Trans. 2005 Nov;33(Pt 5):1029-32
references.pmid: 16246038
references.citation: Bioessays. 2005 Oct;27(10):999-1010
references.pmid: 16163709
references.citation: Curr Opin Struct Biol. 2006 Feb;16(1):127-36
references.pmid: 16442279
references.citation: Peptides. 2006 Jun;27(6):1420-5
references.pmid: 16293343
references.citation: Science. 2005 Aug 12;309(5737):1078-83
references.pmid: 16099987
references.citation: Nature. 2005 Oct 13;437(7061):1032-7
references.pmid: 16136080
references.citation: Inorg Chem. 2001 Jul 2;40(14):3579-87
references.pmid: 11421709
references.citation: J Neurochem. 2005 May;93(3):560-70
references.pmid: 15836615
references.citation: Am J Physiol Endocrinol Metab. 2008 May;294(5):E827-32
references.pmid: 18285524
references.citation: Prog Brain Res. 2006;153:155-74
references.pmid: 16876574
references.citation: J Neuroendocrinol. 2008 Jun;20(6):880-4
references.pmid: 18601712
references.citation: Mol Psychiatry. 2005 Feb;10(2):132-46
references.pmid: 15630408
references.citation: Bioinformatics. 2009 Oct 1;25(19):2466-72
references.pmid: 19648136
references.citation: Med Hypotheses. 2009 Mar;72(3):297-305
references.pmid: 19046822
references.citation: Biosystems. 1996;39(1):19-24
references.pmid: 8735384
references.citation: Phys Rev Lett. 1994 Dec 5;73(23):3169-72
references.pmid: 10057305
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):788-91
references.pmid: 12540826
references.citation: PLoS Biol. 2004 Nov;2(11):e369
references.pmid: 15510229
references.citation: Biochem Pharmacol. 2007 Dec 3;74(11):1652-64
references.pmid: 17897631
references.citation: FEBS Lett. 2008 Apr 9;582(8):1266-70
references.pmid: 18282479
references.citation: J Comput Aided Mol Des. 2006 Oct-Nov;20(10-11):647-71
references.pmid: 17124629
references.citation: Obes Rev. 2008 May;9(3):236-45
references.pmid: 18034789
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):11980-5
references.pmid: 14530388
references.citation: Behav Genet. 2005 Jan;35(1):85-92
references.pmid: 15674535
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11747-52
references.pmid: 19564605
references.citation: Plant Mol Biol. 2005 Sep;59(1):151-64
references.pmid: 16217609
references.citation: Endocrinology. 1993 Jan;132(1):199-204
references.pmid: 7678213
references.citation: Q J Exp Psychol (Hove). 2008 Jun;61(6):944-57
references.pmid: 18470824
references.citation: Recent Pat Cardiovasc Drug Discov. 2007 Jun;2(2):100-9
references.pmid: 18221108
references.citation: J Biomed Discov Collab. 2007 Oct 03;2:5
references.pmid: 17915020
references.citation: Nature. 2002 Nov 14;420(6912):231-7
references.pmid: 12432408
references.citation: FEMS Microbiol Rev. 1998 Oct;22(4):277-304
references.pmid: 10357579
references.citation: Nat Rev Drug Discov. 2004 Apr;3(4):353-9
references.pmid: 15060530
references.citation: Obesity (Silver Spring). 2006 Aug;14 Suppl 5:197S-200S
references.pmid: 17021366
references.citation: Proc Natl Acad Sci U S A. 2007 May 1;104(18):7361-6
references.pmid: 17449635
references.citation: Curr Drug Targets CNS Neurol Disord. 2005 Aug;4(4):331-47
references.pmid: 16101553
references.citation: Curr Med Chem. 2009;16(3):258-66
references.pmid: 19149576
references.citation: Health Aff (Millwood). 2006 Mar-Apr;25(2):420-8
references.pmid: 16522582
references.citation: J Health Econ. 2003 Mar;22(2):151-85
references.pmid: 12606142
references.citation: Prog Biophys Mol Biol. 2004 Jun-Jul;85(2-3):235-60
references.pmid: 15142746
references.citation: Mol Psychiatry. 2001 Nov;6(6):620-4
references.pmid: 11673789
references.citation: Science. 1977 Jun 10;196(4295):1161-6
references.pmid: 860134
references.citation: Nat Biotechnol. 2009 Feb;27(2):157-67
references.pmid: 19204698
references.citation: J Comput Aided Mol Des. 2006 Dec;20(12):773-88
references.pmid: 17051340
references.citation: FEBS Lett. 2007 Jul 31;581(19):3675-80
references.pmid: 17433306
references.citation: Brain Lang. 2002 Apr-Jun;81(1-3):205-23
references.pmid: 12081393
references.citation: J Neuroendocrinol. 1999 Apr;11(4):307-14
references.pmid: 10223285
references.citation: Bioessays. 1998 Aug;20(8):683-5
references.pmid: 9780843
references.citation: Proc AMIA Symp. 2000;:285-9
references.pmid: 11079890
references.citation: Health Care Manage Rev. 1983 Spring;8(2):17-26
references.pmid: 6862879
references.citation: J Endocrinol. 2006 Oct;191(1):179-88
references.pmid: 17065401
references.citation: Nat Biotechnol. 2007 Oct;25(10):1119-26
references.pmid: 17921997
references.citation: J Am Chem Soc. 2007 May 30;129(21):6807-11
references.pmid: 17480075
references.citation: Pharmacol Ther. 2009 Nov;124(2):248-57
references.pmid: 19664655
references.citation: Science. 2002 Oct 25;298(5594):824-7
references.pmid: 12399590
references.citation: Nat Struct Mol Biol. 2004 Dec;11(12):1160-2
references.pmid: 15578054
references.citation: Clin Chim Acta. 2002 Dec;326(1-2):3-25
references.pmid: 12417094
references.citation: Acta Biotheor. 1994 Sep;42(2-3):167-79
references.pmid: 7976062