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

Abstract

Background Glycoproteomics 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. 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. Design Forty-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. Results At 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. Conclusions Based 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 registration NCT02298725 at clinicaltrials.gov; https://clinicaltrials.gov/ct2/show/NCT02298725.

Plasma N-glycome shows continuous deterioration as the diagnosis of insulin resistance approaches

“…One study found dietary habits influencing interesting changes in plasma N-glycosylation. 36 Increased sialylation was positively associated with a healthier diet, which is opposite to the commonly observed higher abundance of highly sialylated (trisialylated and tetrasialylated) glycans in individuals with various diseases. Since IR is a known driving factor for T2DM development and its key feature, in addition to previous findings, this study investigated whether plasma N-glycome is predictive of first clinical diagnosis of impaired glucose metabolism, incident IR or T2DM in 534 individuals (89 incident IR/T2DM cases, 445 controls) from the TwinsUK cohort with independent replication.…”

“…Apart from being associated with various diseases and disorders, plasma N-glycosylation has been thoroughly examined in association with lifestyle factors, such as smoking, 33 exercise, 34 sleep 35 and dietary habits. 36 While smoking influenced increase in complexity of glycans, 33 which is associated with a proinflammatory-like glycosylation profile, moderate to vigorous exercise positively affected the plasma glycosylation profile of older female individuals despite them being diagnosed with metabolic syndrome by decreasing levels of triantennary and tetra-antennary glycans, 34 both hallmarks of complex plasma glycoprofile. Interestingly, higher abundance of biantennary glycan structures with core fucose and one or two sialic acid residues was observed in patients with rapid eye movement sleep behavior disorder when compared with healthy controls.…”

Glycosylation Biomarkers Associated with Age-Related Diseases and Current Methods for Glycan Analysis

“…A better understanding of the interaction between nutrition and ageing is essential to unravel the mechanisms responsible for these positive/negative effects, to identify diet components promoting the quality of life in old age and to contribute to the prevention of late-life disabilities [ 14 ]. Few studies have shown how the dietary patterns in humans affect glycosylation, however there is evidence that diet may influence disease state by altering glycosylation [ 15 ].…”

Imaging Mass Spectrometry Reveals Alterations in N-Linked Glycosylation That Are Associated With Histopathological Changes in Nonalcoholic Steatohepatitis in Mouse and Human

“…Alterations in glycosylation have been reported in metabolic diseases like fatty liver disease, diabetes, and NASH ( 6 , 20 , 47 , 48 , 49 ). The use of serum glycan markers is the most common method to identify specific N-linked glycan alterations that can be utilized for biomarkers strategies in fatty liver disease and NASH ( 7 , 19 ).…”