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

Valentina L Greto; Ana Cvetko; Tamara Štambuk; Niall J Dempster; Domagoj Kifer; Helena Deriš; Ana Cindrić; Frano Vučković; Mario Falchi; Richard S Gillies; Jeremy W Tomlinson; Olga Gornik; Bruno Sgromo; Tim D Spector; Cristina Menni; Alessandra Geremia; Carolina V Arancibia-Cárcamo; Gordan Lauc

doi:10.1038/s41366-021-00816-3

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

Valentina L Greto, Ana Cvetko, Tamara Štambuk, Niall J Dempster, Domagoj Kifer, Helena Deriš, Ana Cindrić, Frano Vučković, Mario Falchi, Richard S Gillies, Jeremy W Tomlinson, Olga Gornik, Bruno Sgromo, Tim D Spector, Cristina Menni, Alessandra Geremia, Carolina V Arancibia-Cárcamo, Gordan Lauc

Twin Research & Genetic Epidemiology

Research output: Contribution to journal › Article › peer-review

34 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1521-1531
Number of pages	11
Journal	International Journal of Obesity
Volume	45
Issue number	7
Early online date	3 May 2021
DOIs	https://doi.org/10.1038/s41366-021-00816-3
Publication status	Published - Jul 2021

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10.1038/s41366-021-00816-3

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Greto, V. L., Cvetko, A., Štambuk, T., Dempster, N. J., Kifer, D., Deriš, H., Cindrić, A., Vučković, F., Falchi, M., Gillies, R. S., Tomlinson, J. W., Gornik, O., Sgromo, B., Spector, T. D., Menni, C., Geremia, A., Arancibia-Cárcamo, C. V., & Lauc, G. (2021). Extensive weight loss reduces glycan age by altering IgG N-glycosylation. International Journal of Obesity, 45(7), 1521-1531. https://doi.org/10.1038/s41366-021-00816-3

@article{94a17a14053241748ece4d247c6613da,

title = "Extensive weight loss reduces glycan age by altering IgG N-glycosylation",

abstract = "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.",

author = "Greto, {Valentina L} and Ana Cvetko and Tamara {\v S}tambuk and Dempster, {Niall J} and Domagoj Kifer and Helena Deri{\v s} and Ana Cindri{\'c} and Frano Vu{\v c}kovi{\'c} and Mario Falchi and Gillies, {Richard S} and Tomlinson, {Jeremy W} and Olga Gornik and Bruno Sgromo and Spector, {Tim D} and Cristina Menni and Alessandra Geremia and Arancibia-C{\'a}rcamo, {Carolina V} and Gordan Lauc",

note = "Funding Information: Conflict of interest Tamara {\v S}tambuk Declaration of interest: Dr. {\v S}tambuk reports that she is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Helena Deri{\v s} Declaration of interest: Helena Deri{\v s} reports that she is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Ana Cindri{\'c} Declaration of interest: Ana Cindri{\'c} reports that she is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Frano Vu{\v c}kovi{\'c} Declaration of interest: Dr. Vu{\v c}kovi{\'c} reports that he is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Olga Gornik Declaration of interest: Dr. Gornik reports that she is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Alessandra Geremia Declaration of interest: Dr. Geremia reports grants from Wellcome Trust, grants from NIHR research capability fund, during the conduct of the study; other from UCB Pharma, outside the submitted work. Gordan Lauc Declaration of interest: Dr. Lauc reports that he is founder and owner of Genos LTD Zagreb; In addition, Dr. Lauc has multiple patents in the field of glycoscience pending or issued. Valentina L. Greto, Ana Cvetko, Niall J. Dempster, Mario Falchi, Cristina Menni, Jeremy W. Tomlinson, Domagoj Kifer, Bruno Sgromo, Richard S. Gillies, Tim Spector, Cristina Menni, Carolina V. Arancibia-C{\'a}rcamo Declarations of interest: none. Funding Information: Acknowledgements This research was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors thank Rachel Franklin, Michelle Haylock, James Chi-venga, Roxanne Williams and the BRC Oxford GI Biobank for sample collection. The authors thank all the patients who took part in this study. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jul,

doi = "10.1038/s41366-021-00816-3",

language = "English",

volume = "45",

pages = "1521--1531",

journal = "International Journal of Obesity",

issn = "0307-0565",

publisher = "Springer Nature [academic journals on nature.com]",

number = "7",

}

Greto, VL, Cvetko, A, Štambuk, T, Dempster, NJ, Kifer, D, Deriš, H, Cindrić, A, Vučković, F, Falchi, M, Gillies, RS, Tomlinson, JW, Gornik, O, Sgromo, B, Spector, TD , Menni, C, Geremia, A, Arancibia-Cárcamo, CV & Lauc, G 2021, 'Extensive weight loss reduces glycan age by altering IgG N-glycosylation', International Journal of Obesity, vol. 45, no. 7, pp. 1521-1531. https://doi.org/10.1038/s41366-021-00816-3

TY - JOUR

T1 - Extensive weight loss reduces glycan age by altering IgG N-glycosylation

AU - Greto, Valentina L

AU - Cvetko, Ana

AU - Štambuk, Tamara

AU - Dempster, Niall J

AU - Kifer, Domagoj

AU - Deriš, Helena

AU - Cindrić, Ana

AU - Vučković, Frano

AU - Falchi, Mario

AU - Gillies, Richard S

AU - Tomlinson, Jeremy W

AU - Gornik, Olga

AU - Sgromo, Bruno

AU - Spector, Tim D

AU - Menni, Cristina

AU - Geremia, Alessandra

AU - Arancibia-Cárcamo, Carolina V

AU - Lauc, Gordan

N1 - Funding Information: Conflict of interest Tamara Štambuk Declaration of interest: Dr. Štambuk reports that she is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Helena Deriš Declaration of interest: Helena Deriš reports that she is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Ana Cindrić Declaration of interest: Ana Cindrić reports that she is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Frano Vučković Declaration of interest: Dr. Vučković reports that he is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Olga Gornik Declaration of interest: Dr. Gornik reports that she is an employee of Genos Glycoscience Research Laboratory which offers commercial service of glycomic analysis and has several patents in the field. Alessandra Geremia Declaration of interest: Dr. Geremia reports grants from Wellcome Trust, grants from NIHR research capability fund, during the conduct of the study; other from UCB Pharma, outside the submitted work. Gordan Lauc Declaration of interest: Dr. Lauc reports that he is founder and owner of Genos LTD Zagreb; In addition, Dr. Lauc has multiple patents in the field of glycoscience pending or issued. Valentina L. Greto, Ana Cvetko, Niall J. Dempster, Mario Falchi, Cristina Menni, Jeremy W. Tomlinson, Domagoj Kifer, Bruno Sgromo, Richard S. Gillies, Tim Spector, Cristina Menni, Carolina V. Arancibia-Cárcamo Declarations of interest: none. Funding Information: Acknowledgements This research was funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors thank Rachel Franklin, Michelle Haylock, James Chi-venga, Roxanne Williams and the BRC Oxford GI Biobank for sample collection. The authors thank all the patients who took part in this study. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85105199355&partnerID=8YFLogxK

U2 - 10.1038/s41366-021-00816-3

DO - 10.1038/s41366-021-00816-3

M3 - Article

C2 - 33941843

SN - 0307-0565

VL - 45

SP - 1521

EP - 1531

JO - International Journal of Obesity

JF - International Journal of Obesity

IS - 7

ER -

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

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