title: Whole serum 3D LC-nESI-FTMS quantitative proteomics reveals sexual dimorphism in the milieu intérieur of overweight and obese adults.
abstract: Linking gender-specific differences to the molecular etiology of obesity has been largely based on genomic and transcriptomic evidence lacking endophenotypic insight and is not applicable to the extracellular fluid compartments, or the milieu intérieur, of the human body. To address this need, this study profiled the whole serum proteomes of age-matched nondiabetic overweight and obese females (n = 28) and males (n = 31) using a multiplex design with pooled biological and technical replicates. To bypass basic limitations of immunodepletion-based strategies, subproteome enrichment by size-exclusion chromatography (SuPrE-SEC) followed by iTRAQ 2D-LC-nESI-FTMS analysis was used. The study resulted in the reproducible analysis of 2472 proteins (peptide FDR < 5%, q < 0.05). A total of 248 proteins exhibited significant modulation between men and women (p < 0.05) that mapped to pathways associated with β-estradiol, lipid and prostanoid metabolism, vitamin D function, immunity/inflammation, and the complement and coagulation cascades. This novel endophenotypic signature of gender-specific differences in whole serum confirmed and expanded the results of previous physiologic and pharmacologic studies exploring sexual dimorphism at the genomic and transcriptomic level in tissues and cells. Conclusively, the multifactorial and pleiotropic nature of human obesity exhibits sexual dimorphism in the circulating proteome of importance to clinical study design.
authors: Biomarkers Research Program, Biochemistry Department, College of Science, ‡Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, §Center of Excellence in Biotechnology Research, and #Department of Clinical Pharmacy, College of Pharmacy, King Saud University , Riyadh 12372, Kingdom of Saudi Arabia.
authors: Nasser M
authors: NM
authors: Al-Daghri
authors: Omar S
authors: OS
authors: Al-Attas
authors: Harvey E
authors: HE
authors: Johnston
authors: Akul
authors: A
authors: Singhania
authors: Majed S
authors: MS
authors: Alokail
authors: Khalid M
authors: KM
authors: Alkharfy
authors: Sherif H
authors: SH
authors: Abd-Alrahman
authors: Shaun L
authors: SL
authors: Sabico
authors: Theodoros I
authors: TI
authors: Roumeliotis
authors: Antigoni
authors: A
authors: Manousopoulou-Garbis
authors: Paul A
authors: PA
authors: Townsend
authors: Christopher H
authors: CH
authors: Woelk
authors: George P
authors: GP
authors: Chrousos
authors: Spiros D
authors: SD
authors: Garbis
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002850:Chromatography, Gel / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000378:metabolism; D050177:Overweight / Q000097:blood* / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D012727:Sex Characteristics; D012737:Sex Factors; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D059467:Transcriptome
chemical_list: D001798:Blood Proteins
keywords: FT-MS; cardiovascular physiology; depletion-free; iTRAQ; multiplex quantitative proteomics; sexual dimorphism; size exclusion chromatography; subproteome enrichment; whole serum milieu intérieur