Abstract

BackgroundGlycoproteomics deals with glycoproteins that are formed by post-translational modification when sugars (like fucose and sialic acid) are attached to protein. Glycosylation of proteins influences function, but whether glycosylation is altered by diet is unknown.ObjectiveTo evaluate the effect of consuming a diet based on the Dietary Guidelines for Americans on circulating glycoproteins that have previously been associated with cardiometabolic diseases.DesignForty-four women, with one or more metabolic syndrome characteristics, completed an 8-week randomized controlled feeding intervention (n = 22) consuming a diet based on the Dietary Guidelines for Americans (DGA 2010); the remaining consumed a ‘typical American diet’ (TAD, n = 22). Fasting serum samples were obtained at week0 (baseline) and week8 (post-intervention); 17 serum proteins were chosen for targeted analyses. Protein standards and serum samples were analyzed in a UHPLC-MS protocol to determine peptide concentration and their glycan (fucosylation or sialylation) profiles. Data at baseline were used in correlational analyses; change in proteins and glycans following intervention were used in non-parametric analyses.ResultsAt baseline, women with more metabolic syndrome characteristics had more fucosylation (total di-fucosylated proteins: p = 0.045) compared to women with a lesser number of metabolic syndrome characteristics. Dietary refined grain intake was associated with increased total fucosylation (ρ = − 0.530, p < 0.001) and reduced total sialylation (ρ = 0.311, p = 0.042). After the 8-week intervention, there was higher sialylation following the DGA diet (Total di-sialylated protein p = 0.018, poly-sialylated orosomucoid p = 0.012) compared to the TAD diet.ConclusionsBased on this study, glycosylation of proteins is likely affected by dietary patterns; higher sialylation was associated with a healthier diet pattern. Altered glycosylation is associated with several diseases, particularly cancer and type 2 diabetes, and this study raises the possibility that diet may influence disease state by altering glycosylation.Clinical trial registrationNCT02298725 at clinicaltrials.gov; https://clinicaltrials.gov/ct2/show/NCT02298725.

Highlights

  • The Dietary Guidelines for Americans (DGA), a resource that guides what constitutes a healthy diet, is aimed at preventing chronic illnesses [1]

  • We used targeted glycoproteomic analyses, a branch of proteomics that measures glycoproteins, to evaluate selected serum proteins that are associated with cardiometabolic disease risks

  • We present glycoproteome data at baseline in women who had one or more characteristics of metabolic syndrome, as well as following an 8-week controlled feeding intervention where the women either followed a diet based on the Dietary Guidelines for Americans 2010 (DGA) or a typical American diet (TAD)

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Summary

Introduction

The Dietary Guidelines for Americans (DGA), a resource that guides what constitutes a healthy diet, is aimed at preventing chronic illnesses [1] These guidelines have only been tested twice in a controlled feeding setting, which is considered the gold standard in nutrition research [2]. We recently evaluated the effect of consuming a DGA based diet for twice that duration (8 weeks) on insulin resistance and circulating lipids [4]. While recent efforts have focused on identifying metabolomics-based biomarkers of healthy dietary patterns in large-scale epidemiological studies [5], no study to date has reported changes in metabolomics biomarkers following a controlled feeding trial of the Dietary Guidelines for Americans. Objective To evaluate the effect of consuming a diet based on the Dietary Guidelines for Americans on circulating glycoproteins that have previously been associated with cardiometabolic diseases. Clinical trial registration NCT02298725 at clinicaltrials.gov; https://clinicaltrials.gov/ct2/show/NCT02​298725

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