Extensive weight loss reduces glycan age by altering IgG N-glycosylation

• Published in: International Journal of Obesity 2021-07, Vol.45 (7), p.1521-1531
• Main Authors: Greto, Valentina L., Cvetko, Ana, Štambuk, Tamara, Dempster, Niall J., Kifer, Domagoj, Deriš, Helena, Cindrić, Ana, Vučković, Frano, Falchi, Mario, Gillies, Richard S., Tomlinson, Jeremy W., Gornik, Olga, Sgromo, Bruno, Spector, Tim D., Menni, Cristina, Geremia, Alessandra, Arancibia-Cárcamo, Carolina V., Lauc, Gordan
• Format: Article
• Language: English
• Subjects: 631/250; 631/45/72/1202; 692/163/2743/393; 82; 82/16; Adult; Age; Aging; Aging - physiology; Bariatric Surgery; Body Mass Index; Body weight loss; Calories; Diet; Epidemiology; Female; Gastrointestinal surgery; Global health; Glycan; Glycosylation; Health Promotion and Disease Prevention; Humans; Hypocaloric diet; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - chemistry; Inflammation; Internal Medicine; Longitudinal Studies; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Morbidity; N-glycans; Nutrient deficiency; Obesity; Obesity - blood; Obesity - metabolism; Polysaccharides; Public Health; Surgery; Twins; Weight control; Weight loss; Weight Loss - physiology; Weight reduction
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-021-00816-3

Background Obesity, a major global health problem, is associated with increased cardiometabolic morbidity and mortality. Protein glycosylation is a frequent posttranslational modification, highly responsive to inflammation and ageing. The prospect of biological age reduction, by changing glycosylation patterns through metabolic intervention, opens many possibilities. We have investigated whether weight loss interventions affect inflammation- and ageing-associated IgG glycosylation changes, in a longitudinal cohort of bariatric surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal twins cohort. Methods IgG N-glycans were chromatographically profiled in 37 obese patients, subjected to low-calorie diet, followed by bariatric surgery, across multiple timepoints. Similarly, plasma-derived IgG N-glycan traits were longitudinally monitored in 1680 participants from the TwinsUK cohort. Results Low-calorie diet induced a marked decrease in the levels of IgG N-glycans with bisecting GlcNAc, whose higher levels are usually associated with ageing and inflammatory conditions. Bariatric surgery resulted in extensive alterations of the IgG N-glycome that accompanied progressive weight loss during 1-year follow-up. We observed a significant increase in digalactosylated and sialylated glycans, and a substantial decrease in agalactosylated and core fucosylated IgG N-glycans (adjusted p value range 7.38 × 10 −04 –3.94 × 10 −02 ). This IgG N-glycan profile is known to be associated with a younger biological age and reflects an enhanced anti-inflammatory IgG potential. Loss of BMI over a 20 year period in the TwinsUK cohort validated a weight loss-associated agalactosylation decrease (adjusted p value 1.79 × 10 −02 ) and an increase in digalactosylation (adjusted p value 5.85 × 10 −06 ). Conclusions Altogether, these findings highlight that weight loss substantially affects IgG N-glycosylation, resulting in reduced glycan and biological age. Highlights Obesity is associated with inflammation-related agalactosylated and bisected IgG glycoforms. IgG bisected glycoforms decrease after low-calorie diet. IgG galactosylation and sialylation increase after bariatric surgery-induced weight loss. Progressive decrease of BMI is associated with increased IgG galactosylation, implying a reduction of biological age.