Sex-specific correlation of IGFBP-2 and IGFBP-3 with vitamin D status in adults with obesity: a cross-sectional serum proteomics study

Abstract

Objective: Subjects with low vitamin D levels are at risk of cardiometabolic disease. The aim of this study was to identify novel serological markers linking vitamin D status with cardiometabolic profile in non-diabetic adults with obesity. Methods: For the discovery phase, we used quantitative serum proteomics in sex-matched, age-matched and BMI-matched subjects with obesity [BMI: 25–35 kg/m^2] and low [25(OH)D < 50 nmol/L] vs. high vitamin D status [25(OH)D > 50 nmol/L] (n = 16). For the validation phase, we performed ELISA in a larger cohort with similar characteristics (n = 179). Results: We identified 423 and 549 differentially expressed proteins in the high vs. low vitamin D groups of the male and female cohorts, respectively. The small molecule biochemistry protein networks and the glycolysis|gluconeogenesis pathway were significantly enriched in the DEPs of both sexes. As surrogate markers to these processes, the insulin-like growth factor binding protein -2 (IGFBP-2) was upregulated in males, whereas IGFBP-3 was upregulated in females from the high Vitamin D status. This sex-specific trend was confirmed using Luminex ELISA to an independent but clinically analogous cohort of males (n = 84, p = 0.002) and females (n = 95, p = 0.03). Conclusions: The high Vitamin D status correlated with the serological upregulation of IGFBP-2 in males and IGFBP-3 in females with obesity and may constitute surrogate markers of risk reduction of cardiometabolic disease.

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© 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received: 27 May 2018. Revised: 20 August 2018. Accepted: 10 September 2018. Published online: 04 October 2018. Funding: The Deanship of Scientific Research, Prince Mutaib Chair for Biomarkers of Osteoporosis in King Saud University, Riyadh, Saudi Arabia. JT was supported by the China Scholarship Council and the China Postdoctoral Science Foundation (2013T60260). These authors are contributed equally: Nasser M. Al-Daghri, Antigoni Manousopoulou. Author Contributions: N.A.D., A.M., G.P.C., and S.D.G. concept and clinical design; A.M., D.G.B., M.F., J.T., and A.A. performed proteomics work; S.Y., Y.A.S., and S.S. performed verification work; A.M., D.G.B., and S.D.G. contributed new reagents and analytic tools; A.M., S.Y., S.S. and S.D.G. analyzed data; N.A.D., O.A.A., G.P.C., and S.D.G. supervised research; A.M. and S.D.G. writing-original draft; N.A.D., A.M., S.S., G.P.C. and S.D.G. writing-review and editing. The authors declare that they have no conflict of interest.

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