Differential Plasma N-Glycopeptides in Monozygotic Twin Pairs Discordant for BMI
Background: N-glycosylation of proteins is a complex non-template post-translational modification, which influences protein function and is very sensitive to changes in physiology. Cardiometabolic diseases are associated with aberrant N-glycosylation of proteins, for which associations may not be vi...
Saved in:
| Published in: | Obesity (Silver Spring, Md.) Vol. 31; pp. 261 - 262 |
|---|---|
| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Silver Spring
Blackwell Publishing Ltd
01-11-2023
|
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Background: N-glycosylation of proteins is a complex non-template post-translational modification, which influences protein function and is very sensitive to changes in physiology. Cardiometabolic diseases are associated with aberrant N-glycosylation of proteins, for which associations may not be visible at the protein level. Here, we used targeted quantitative glycoproteomics to study N-glycosylation of plasma proteins in acquired obesity. Methods: From plasma samples of 48 BMI-discordant monozygotic twin pairs, a study design of genetically matched controls of leaner and heavier groups (intrapair difference BMI >2.5 kg/m2 with 17.8 kg mean Aweight), we performed glycopeptide identification and quantitation by mass spectrometry, including in-tandem total protein quantitation to determine the extent of N-glycosylation changes relative to the protein-backbone level. We used a linear mixed-model to identify differential protein and glycopeptide levels. Results: We identified 230 proteins of which 51 proteins were different (p < 0.05) between leaner and heavier со-twins. We isolated and quantified 8000 N-glycopeptide ions. Of those 2025 differential N-glycopeptides (p < 0.05) between leaner and heavier со-twins, we elucidated peptide sequence, N-glycosylation site, glycan composition and proposed glycan structures of 32 glycopeptides. Haptoglobin showed significant protein upregulation (FC 1.11, p = 0.004) in heavier со-twins along with seven different upregulated glycan compositions at the N-glycosylation site Asn241, revealing increased microheterogeneity and increased sialylation. The complement protein C3 was significantly upregulated (FC 1.08, p = 0.008) along with one upregulated glycopeptide at Asn85. Finally, many glycopeptides were upregulated despite insignificant differences to proteinbackbone plasma levels. Conclusions: Our findings suggest that the differential N-glycosylation of plasma proteins, including inflammatory proteins haptoglobin and C3, can be linked to obesity. |
|---|---|
| ISSN: | 1930-7381 1930-739X |