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Whole serum 3D LC-nESI-FTMS quantitative proteomics reveals sexual dimorphism in the Milieu Interieur of overweight and obese adults

Whole serum 3D LC-nESI-FTMS quantitative proteomics reveals sexual dimorphism in the Milieu Interieur of overweight and obese adults
Whole serum 3D LC-nESI-FTMS quantitative proteomics reveals sexual dimorphism in the Milieu Interieur of overweight and obese adults
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 ?-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.
FT-MS, cardiovascular physiology, depletion-free, iTRAQ, multiplex quantitative proteomics, sexual dimorphism, size exclusion chromatography, subproteome enrichment, whole serum milieu intérieur
1535-3893
5094-5105
Al-Daghri, N.
21272a0a-ffb4-4380-a04f-e4d9cc2e7f3c
Attas, O.
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Johnston, H.
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Singhania, A.
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Alokail, M.
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Alkharfy, K.
90375514-aa03-48ae-8bbb-9c2c5a9ce411
Abd-Alrahman, S.
17c01056-f9d7-4740-98db-5f6e4ff8c05a
Sabico, S.
8672f10e-65d7-412d-b616-5e6e625c9be5
Roumeliotis, T.
f4ae258d-23c9-4440-af44-15f572435fb2
Manousopoulou, A.
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Townsend, Paul A.
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Woelk, C.H.
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Chrousos, G.
078418dc-70ff-4436-bb30-9deb43856e2b
Garbis, S. D.
7067fd19-50c9-4d42-9611-f370289470bd
Al-Daghri, N.
21272a0a-ffb4-4380-a04f-e4d9cc2e7f3c
Attas, O.
4cb7dec9-090e-4718-9aab-36eae5c9514f
Johnston, H.
8d4500ff-fec8-47ef-b766-798689948cd6
Singhania, A.
9a5f2c6b-fc46-4223-bcae-de70bf14da6b
Alokail, M.
7adcf7eb-1fbf-4dc5-8f28-7b7217f0ca25
Alkharfy, K.
90375514-aa03-48ae-8bbb-9c2c5a9ce411
Abd-Alrahman, S.
17c01056-f9d7-4740-98db-5f6e4ff8c05a
Sabico, S.
8672f10e-65d7-412d-b616-5e6e625c9be5
Roumeliotis, T.
f4ae258d-23c9-4440-af44-15f572435fb2
Manousopoulou, A.
9a5e4e75-cea9-4d0b-91c8-0fa2af02632f
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Woelk, C.H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
Chrousos, G.
078418dc-70ff-4436-bb30-9deb43856e2b
Garbis, S. D.
7067fd19-50c9-4d42-9611-f370289470bd

Al-Daghri, N., Attas, O., Johnston, H., Singhania, A., Alokail, M., Alkharfy, K., Abd-Alrahman, S., Sabico, S., Roumeliotis, T., Manousopoulou, A., Townsend, Paul A., Woelk, C.H., Chrousos, G. and Garbis, S. D. (2014) Whole serum 3D LC-nESI-FTMS quantitative proteomics reveals sexual dimorphism in the Milieu Interieur of overweight and obese adults. Journal of Proteome Research, 13 (11), 5094-5105. (doi:10.1021/pr5003406).

Record type: Article

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 ?-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.

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More information

e-pub ahead of print date: 29 July 2014
Keywords: FT-MS, cardiovascular physiology, depletion-free, iTRAQ, multiplex quantitative proteomics, sexual dimorphism, size exclusion chromatography, subproteome enrichment, whole serum milieu intérieur
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 379210
URI: https://eprints.soton.ac.uk/id/eprint/379210
ISSN: 1535-3893
PURE UUID: c1e31049-7b73-4ca8-bb40-e7ac6d73a9ab
ORCID for S. D. Garbis: ORCID iD orcid.org/0000-0002-1050-0805

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Date deposited: 18 Jul 2015 14:17
Last modified: 05 Nov 2019 01:41

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Contributors

Author: N. Al-Daghri
Author: O. Attas
Author: H. Johnston
Author: A. Singhania
Author: M. Alokail
Author: K. Alkharfy
Author: S. Abd-Alrahman
Author: S. Sabico
Author: T. Roumeliotis
Author: A. Manousopoulou
Author: Paul A. Townsend
Author: C.H. Woelk
Author: G. Chrousos
Author: S. D. Garbis ORCID iD

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