Diet affects glycosylation of serum proteins in women at risk for cardiometabolic disease

Authors: KIM, TYLER - University Of California, Davis; XIE, YIXUAN - University Of California, Davis; LI, QIONGYU - University Of California, Davis; Artegoitia Etchev, Virginia; LEBRILLA, CARLITO - University Of California, Davis; Keim, Nancy; ADAMS, SEAN - University Of California, Davis; KRISHNAN, SRIDEVI - University Of California, Davis

Submitted to: European Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2021
Publication Date: 3/26/2021
Citation: Kim, T., Xie, Y., Li, Q., Artegoitia Etchev, V.M., Lebrilla, C., Keim, N.L., Adams, S., Krishnan, S. 2021. Diet affects glycosylation of serum proteins in women at risk for cardiometabolic disease. European Journal of Nutrition. 60:3727-3741. https://doi.org/10.1007/s00394-021-02539-7.
DOI: https://doi.org/10.1007/s00394-021-02539-7

Interpretive Summary: Identifying biomarkers that are associated with dietary patterns is an important goal for advancing precision nutrition, but very few controlled feeding trials have been conducted to enable this endeavor. In a study conducted by ARS scientists in Davis CA, study volunteers ate either a controlled diet plan representative of the Dietary Guidelines for Americans or a more typical American diet. Using information collected during this study, associations were sought between their habitual diets and/or their responses to the diet intervention with proteins in the general circulation that have undergone cellular transformation by the attachment of strings of sugar molecules, known as the glycoproteome. We found that certain proteins glycoproteins were associated with a healthier diet pattern. This is the first study to document that the glycoproteome profile of serum proteins could act as a biomarker for diet patterns consumed by humans. Further study of the glycoproteome is needed to solidify knowledge about its relationship with the diet, and to better understand the role of these proteins in cardiometabolic disease processes.

Technical Abstract: Glycoproteomics, a branch of proteomics, deals with glycoproteins that are formed by post-translational modification (PTM) when sugars (glycans such as fucose and sialic acid) are attached to protein. PTM determines important structural and functional aspects of proteins, and some specific glycoproteins are associated with cardiometabolic health. The objective of this study was to evaluate the effect of consuming a diet based on the Dietary Guidelines for Americans on circulating proteins that have previously been associated with cardiometabolic diseases. Forty-four women, with one or more metabolic syndrome characteristics, completed an 8-wk randomized controlled feeding intervention, n = 22 consumed a diet based on the Dietary Guidelines for Americans (DGA 2010), the remaining n = 22 consumed a ‘typical American diet’ (TAD) designed using NHANES data. Serum samples were obtained at wk0 (baseline) and wk8 (post-intervention). 17 serum proteins were chosen for the 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, and change in proteins and glycans following the intervention were used in non-parametric analyses. At baseline, women with fewer metabolic syndrome characteristics had more sialylation (total poly-sialylated proteins: p=0.015) compared to women with a greater number of metabolic syndrome characteristics. Habitual refined grain intake was associated with increased total fucosylation (Spearman’s rho = 0.311, p = 0.042). After the 8-wk intervention, there was higher sialylation of proteins following the DGA diet (Total di-sialylated protein p = 0.018, poly-sialylated orosomucoid p = 0.012) compared to the TAD diet. Based on this study, PTM of proteins may be affected by dietary pattern, higher sialylation was associated with healthier diet pattern. The glycoproteome profile of serum proteins could act as a biomarker for diet patterns. In addition, they could also be a link between diet composition and health, since PTM of proteins can affect the function these chosen proteins have in cardiometabolic disease processes.