Alterations in plasma protein N-glycosylation after caloric restriction and bariatric surgery

Background: Protein glycosylation is an enzymatic process known to reflect an individual's physiologic state and changes thereof. The impact of metabolic interventions on plasma protein N-glycosylation has only been sparsely investigated. Objective: To examine alterations in plasma protein N-glycosylation following changes in caloric intake and bariatric surgery. Setting: University of Texas Southwestern Medical Center, US and Oxford University Hospitals, UK. Methods: This study included 2 independent patient cohorts that recruited 10 and 37 individuals with obesity undergoing a period of caloric restriction followed by bariatric surgery. In both cohorts, clinical data were collated, and the composition of plasma protein N-glycome was analyzed chromatographically. Linear mixed models adjusting for age, sex, and multiple testing (false discovery rate <.05) were used to investigate longitudinal changes in glycosylation features and metabolic clinical markers. Results: A low-calorie diet resulted in a decrease in high-branched trigalactosylated and trisialylated plasma N-glycans and a concomitant increase in low-branched N-glycans in both cohorts. Participants from one cohort additionally underwent a washout period during which caloric intake and body weight increased, resulting in reversal of the initial low-calorie diet–related changes in the plasma N-glycome. Immediate postoperative follow-up revealed the same pattern of N-glycosylation changes in both cohorts—an increase in complex, high-branched, antennary fucosylated, extensively galactosylated and sialylated N-glycans and a substantial decline in simpler, low-branched, core fucosylated, bisected, agalactosylated, and asialylated glycans. A 12-month postoperative monitoring in one cohort showed that N-glycan complexity declines while low branching increases. Conclusions: Plasma protein N-glycosylation undergoes extensive alterations following caloric restriction and bariatric surgery. These comprehensive changes may reflect the varying inflammatory status of the individual following dietary and surgical interventions and subsequent weight loss.