title: Dynamics of plasma proteome during leptin-replacement therapy in genetically based leptin deficiency.
abstract: The effects of leptin-replacement therapy on the plasma proteome of three unique adults with genetically based leptin deficiency were studied longitudinally during the course of recombinant human leptin-replacement treatment. Quantitative proteomics analysis was performed in plasma samples collected during four stages: before leptin treatment was initiated, after 1.5 and 6 years of leptin-replacement treatment, and after 7 weeks of temporary interruption of leptin-replacement therapy. Of 500 proteins reliably identified and quantitated in those four stages, about 100 were differentially abundant twofold or more in one or more stages. Synchronous dynamics of abundances of about 90 proteins was observed reflecting both short- and long-term effects of leptin-replacement therapy. Pathways and processes enriched with overabundant synchronous proteins were cell adhesion, cytoskeleton remodeling, cell cycle, blood coagulation, glycolysis, and gluconeogenesis. Plausible common regulators of the above synchronous proteins were identified using transcription regulation network analysis. The generated network included two transcription factors (c-Myc and androgen receptor) that are known to activate each other through a double-positive feedback loop, which may represent a potential molecular mechanism for the long-term effects of leptin-replacement therapy. Our findings may help to elucidate the effects of leptin on insulin resistance.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Center on Pharmacogenomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. vandreev@med.miami.edu
authors.forename: V P
authors.initials: VP
authors.lastname: Andreev
authors.forename: R C
authors.initials: RC
authors.lastname: Dwivedi
authors.forename: G
authors.initials: G
authors.lastname: Paz-Filho
authors.forename: O V
authors.initials: OV
authors.lastname: Krokhin
authors.forename: M-L
authors.initials: ML
authors.lastname: Wong
authors.forename: J A
authors.initials: JA
authors.lastname: Wilkins
authors.forename: J
authors.initials: J
authors.lastname: Licinio
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy; D005943:Gluconeogenesis / Q000235:genetics; D006019:Glycolysis / Q000235:genetics; D020249:Hormone Replacement Therapy; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020543:Proteome / Q000032:analysis / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D020738:Leptin; D020543:Proteome
references.citation: NCHS Data Brief. 2007 Nov;(1):1-8
references.pmid: 19389313
references.citation: Mol Immunol. 2007 Jan;44(4):338-46
references.pmid: 16597464
references.citation: Anal Chem. 2008 Sep 15;80(18):7036-42
references.pmid: 18686972
references.citation: Brief Funct Genomic Proteomic. 2006 Jun;5(2):112-20
references.pmid: 16772272
references.citation: Anal Chem. 2005 Apr 1;77(7):2187-200
references.pmid: 15801753
references.citation: Nat Med. 1997 May;3(5):575-9
references.pmid: 9142131
references.citation: Gene Expr. 1999;7(4-6):311-9
references.pmid: 10440232
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4531-6
references.pmid: 15070752
references.citation: Mol Cell Proteomics. 2005 Sep;4(9):1240-50
references.pmid: 15951569
references.citation: Mol Carcinog. 2009 Feb;48(2):141-9
references.pmid: 18623111
references.citation: J Proteome Res. 2007 Nov;6(11):4363-73
references.pmid: 17924683
references.citation: Genes Dev. 2004 Jul 15;18(14):1753-65
references.pmid: 15256502
references.citation: Mol Cell Proteomics. 2002 Nov;1(11):845-67
references.pmid: 12488461
references.citation: Genome Biol. 2007;8(8):R166
references.pmid: 17697356
references.citation: Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2014-24
references.pmid: 16609010
references.citation: Proteomics. 2005 Feb;5(2):566-71
references.pmid: 15627964
references.citation: Annu Rev Physiol. 2008;70:537-56
references.pmid: 17937601
references.citation: Gene. 1998 Sep 14;217(1-2):151-64
references.pmid: 9841227
references.citation: Semin Cancer Biol. 2006 Jun;16(3):183-92
references.pmid: 16697662
references.citation: Anal Chem. 2005 Oct 1;77(19):6426-34
references.pmid: 16194109
references.citation: Mol Cell Proteomics. 2004 Apr;3(4):311-26
references.pmid: 14718574
references.citation: J Biol Chem. 1996 Mar 8;271(10):5790-4
references.pmid: 8621447
references.citation: Int J Obes (Lond). 2005 Oct;29(10):1175-83
references.pmid: 16030519
references.citation: Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1401-8
references.pmid: 18854428
references.citation: Science. 2002 Mar 1;295(5560):1669-78
references.pmid: 11872831
references.citation: FEBS J. 2005 Jan;272(1):109-19
references.pmid: 15634336
references.citation: N Engl J Med. 1996 Feb 1;334(5):292-5
references.pmid: 8532024
references.citation: Horm Metab Res. 2009 Feb;41(2):142-51
references.pmid: 18726828
references.citation: J Exp Bot. 2006;57(7):1501-8
references.pmid: 16574745
references.citation: Proc Nutr Soc. 2001 Aug;60(3):301-18
references.pmid: 11681805