Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome

Lucy J Goudswaard; Madeleine L Smith; David A Hughes; Roy Taylor; Michael E J Lean; Naveed A. Sattar; Paul Welsh; Alex McConnachie; Jane Blazeby; Chris A Rogers; Karsten Suhre; Shaza B.  Zaghlool; Ingeborg Hers; Nicholas John  Timpson; Laura J Corbin

doi:10.1038/s41598-023-47030-x

Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome

Lucy J Goudswaard^*
, Madeleine L Smith
, David A Hughes
, Roy Taylor
, Michael E J Lean
, Naveed A. Sattar
, Paul Welsh
, Alex McConnachie
, Jane Blazeby
, Chris A Rogers
, Karsten Suhre
, Shaza B. Zaghlool
, Ingeborg Hers
, Nicholas John Timpson
, Laura J Corbin

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

10 Citations (Scopus)

Abstract

Thousands of proteins circulate in the bloodstream; identifying those which associate with weight and intervention-induced weight loss may help explain mechanisms of diseases associated with adiposity. We aimed to identify consistent protein signatures of weight loss across independent studies capturing changes in body mass index (BMI). We analysed proteomic data from studies implementing caloric restriction (Diabetes Remission Clinical trial) and bariatric surgery (By-Band-Sleeve), using SomaLogic and Olink Explore1536 technologies, respectively. Linear mixed models were used to estimate the effect of the interventions on circulating proteins. Twenty-three proteins were altered in a consistent direction after both bariatric surgery and caloric restriction, suggesting that these proteins are modulated by weight change, independent of intervention type. We also integrated Mendelian randomisation (MR) estimates of the effect of BMI on proteins measured by SomaLogic from a UK blood donor cohort as a third line of causal evidence. These MR estimates provided further corroborative evidence for a role of BMI in regulating the levels of six proteins including alcohol dehydrogenase-4, nogo receptor and interleukin-1 receptor antagonist protein. These results indicate the importance of triangulation in interrogating causal relationships; further study into the role of proteins modulated by weight in disease is now warranted.

Original language	English
Article number	21077
Journal	Scientific Reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-023-47030-x
Publication status	Published - 29 Nov 2023

Bibliographical note

Funding Information:
The DiRECT formula diet was donated by Cambridge Weight Plan. Neither organisation had any input into the study design, data analysis or interpretation. We thank the National Health Service (NHS) Primary Care Research Network and Northeast Commissioning Support for their support and valuable input to recruitment. We thank Elaine Butler, Josephine Cooney, Sara-Jane Duffus, and Philip Stewart from the University of Glasgow for providing technical assistance; Helen Pilkington from the Newcastle upon Tyne Hospitals NHS Foundation Trust for providing research nurse support; and Sarah Weeden and Sarah Cadzow from the Robertson Centre for Biostatistics. We thank Wilma Leslie and research dietitians Louise McCombie, George Thom, Naomi Brosnahan and Alison Barnes for their contributions to the collection and transport of samples. We are enormously grateful to the GP practices, health-care professionals, and volunteers for their participation. The By-Band-Sleeve trial is led by JM Blazeby (Chief Investigator) and C Rogers (lead methodologist). We acknowledge the support of all other members of the NIHR By-Band-Sleeve Management Group: Robert C Andrews, John Bessant, James P Byrne, Nicholas Carter, Caroline Clay, Jenny L Donovan, Eleanor Gidman, Graziella Mazza, Mary O’Kane, Barnaby C Reeves, Nicki Salter, Janice L Thompson, Richard Welbourn and Sarah Wordsworth. We also thank all the By-Band-Sleeve contributors including the investigators, research dieticians and nurses, the independent trial steering committee and data monitoring and safety committee. We are grateful to all the patients who participated in this trial. By-Band-Sleeve is in the follow-up phase.

Publisher Copyright:
© 2023, The Author(s).

Access to Document

10.1038/s41598-023-47030-xLicence: CC BY

Handle.net

Persistent link

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research
Gastric Bypass, adjustable gastric Banding or Sleeve gastorectomy surgery to treat severe and complex obesity: a multi-centre randomised controlled trial (The By-Band Sleeve Study) HTA Project No. 09/127/53
Blazeby, J. (Principal Investigator)
1/01/12 → 31/03/23
Project: Research

Cite this

Goudswaard, L. J., Smith, M. L., Hughes, D. A., Taylor, R., Lean, M. E. J., Sattar, N. A., Welsh, P., McConnachie, A., Blazeby, J., Rogers, C. A., Suhre, K., Zaghlool, S. B., Hers, I., Timpson, N. J., & Corbin, L. J. (2023). Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome. Scientific Reports, 13(1), Article 21077. https://doi.org/10.1038/s41598-023-47030-x

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title = "Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome",

abstract = "Thousands of proteins circulate in the bloodstream; identifying those which associate with weight and intervention-induced weight loss may help explain mechanisms of diseases associated with adiposity. We aimed to identify consistent protein signatures of weight loss across independent studies capturing changes in body mass index (BMI). We analysed proteomic data from studies implementing caloric restriction (Diabetes Remission Clinical trial) and bariatric surgery (By-Band-Sleeve), using SomaLogic and Olink Explore1536 technologies, respectively. Linear mixed models were used to estimate the effect of the interventions on circulating proteins. Twenty-three proteins were altered in a consistent direction after both bariatric surgery and caloric restriction, suggesting that these proteins are modulated by weight change, independent of intervention type. We also integrated Mendelian randomisation (MR) estimates of the effect of BMI on proteins measured by SomaLogic from a UK blood donor cohort as a third line of causal evidence. These MR estimates provided further corroborative evidence for a role of BMI in regulating the levels of six proteins including alcohol dehydrogenase-4, nogo receptor and interleukin-1 receptor antagonist protein. These results indicate the importance of triangulation in interrogating causal relationships; further study into the role of proteins modulated by weight in disease is now warranted.",

author = "Goudswaard, \{Lucy J\} and Smith, \{Madeleine L\} and Hughes, \{David A\} and Roy Taylor and Lean, \{Michael E J\} and Sattar, \{Naveed A.\} and Paul Welsh and Alex McConnachie and Jane Blazeby and Rogers, \{Chris A\} and Karsten Suhre and Zaghlool, \{Shaza B.\} and Ingeborg Hers and Timpson, \{Nicholas John\} and Corbin, \{Laura J\}",

note = "Funding Information: The DiRECT formula diet was donated by Cambridge Weight Plan. Neither organisation had any input into the study design, data analysis or interpretation. We thank the National Health Service (NHS) Primary Care Research Network and Northeast Commissioning Support for their support and valuable input to recruitment. We thank Elaine Butler, Josephine Cooney, Sara-Jane Duffus, and Philip Stewart from the University of Glasgow for providing technical assistance; Helen Pilkington from the Newcastle upon Tyne Hospitals NHS Foundation Trust for providing research nurse support; and Sarah Weeden and Sarah Cadzow from the Robertson Centre for Biostatistics. We thank Wilma Leslie and research dietitians Louise McCombie, George Thom, Naomi Brosnahan and Alison Barnes for their contributions to the collection and transport of samples. We are enormously grateful to the GP practices, health-care professionals, and volunteers for their participation. The By-Band-Sleeve trial is led by JM Blazeby (Chief Investigator) and C Rogers (lead methodologist). We acknowledge the support of all other members of the NIHR By-Band-Sleeve Management Group: Robert C Andrews, John Bessant, James P Byrne, Nicholas Carter, Caroline Clay, Jenny L Donovan, Eleanor Gidman, Graziella Mazza, Mary O{\textquoteright}Kane, Barnaby C Reeves, Nicki Salter, Janice L Thompson, Richard Welbourn and Sarah Wordsworth. We also thank all the By-Band-Sleeve contributors including the investigators, research dieticians and nurses, the independent trial steering committee and data monitoring and safety committee. We are grateful to all the patients who participated in this trial. By-Band-Sleeve is in the follow-up phase. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

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Goudswaard, LJ, Smith, ML, Hughes, DA, Taylor, R, Lean, MEJ, Sattar, NA, Welsh, P, McConnachie, A, Blazeby, J, Rogers, CA, Suhre, K, Zaghlool, SB, Hers, I , Timpson, NJ & Corbin, LJ 2023, 'Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome', Scientific Reports, vol. 13, no. 1, 21077. https://doi.org/10.1038/s41598-023-47030-x

TY - JOUR

T1 - Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome

AU - Goudswaard, Lucy J

AU - Smith, Madeleine L

AU - Hughes, David A

AU - Taylor, Roy

AU - Lean, Michael E J

AU - Sattar, Naveed A.

AU - Welsh, Paul

AU - McConnachie, Alex

AU - Blazeby, Jane

AU - Rogers, Chris A

AU - Suhre, Karsten

AU - Zaghlool, Shaza B.

AU - Hers, Ingeborg

AU - Timpson, Nicholas John

AU - Corbin, Laura J

N1 - Funding Information: The DiRECT formula diet was donated by Cambridge Weight Plan. Neither organisation had any input into the study design, data analysis or interpretation. We thank the National Health Service (NHS) Primary Care Research Network and Northeast Commissioning Support for their support and valuable input to recruitment. We thank Elaine Butler, Josephine Cooney, Sara-Jane Duffus, and Philip Stewart from the University of Glasgow for providing technical assistance; Helen Pilkington from the Newcastle upon Tyne Hospitals NHS Foundation Trust for providing research nurse support; and Sarah Weeden and Sarah Cadzow from the Robertson Centre for Biostatistics. We thank Wilma Leslie and research dietitians Louise McCombie, George Thom, Naomi Brosnahan and Alison Barnes for their contributions to the collection and transport of samples. We are enormously grateful to the GP practices, health-care professionals, and volunteers for their participation. The By-Band-Sleeve trial is led by JM Blazeby (Chief Investigator) and C Rogers (lead methodologist). We acknowledge the support of all other members of the NIHR By-Band-Sleeve Management Group: Robert C Andrews, John Bessant, James P Byrne, Nicholas Carter, Caroline Clay, Jenny L Donovan, Eleanor Gidman, Graziella Mazza, Mary O’Kane, Barnaby C Reeves, Nicki Salter, Janice L Thompson, Richard Welbourn and Sarah Wordsworth. We also thank all the By-Band-Sleeve contributors including the investigators, research dieticians and nurses, the independent trial steering committee and data monitoring and safety committee. We are grateful to all the patients who participated in this trial. By-Band-Sleeve is in the follow-up phase. Publisher Copyright: © 2023, The Author(s).

PY - 2023/11/29

Y1 - 2023/11/29

N2 - Thousands of proteins circulate in the bloodstream; identifying those which associate with weight and intervention-induced weight loss may help explain mechanisms of diseases associated with adiposity. We aimed to identify consistent protein signatures of weight loss across independent studies capturing changes in body mass index (BMI). We analysed proteomic data from studies implementing caloric restriction (Diabetes Remission Clinical trial) and bariatric surgery (By-Band-Sleeve), using SomaLogic and Olink Explore1536 technologies, respectively. Linear mixed models were used to estimate the effect of the interventions on circulating proteins. Twenty-three proteins were altered in a consistent direction after both bariatric surgery and caloric restriction, suggesting that these proteins are modulated by weight change, independent of intervention type. We also integrated Mendelian randomisation (MR) estimates of the effect of BMI on proteins measured by SomaLogic from a UK blood donor cohort as a third line of causal evidence. These MR estimates provided further corroborative evidence for a role of BMI in regulating the levels of six proteins including alcohol dehydrogenase-4, nogo receptor and interleukin-1 receptor antagonist protein. These results indicate the importance of triangulation in interrogating causal relationships; further study into the role of proteins modulated by weight in disease is now warranted.

AB - Thousands of proteins circulate in the bloodstream; identifying those which associate with weight and intervention-induced weight loss may help explain mechanisms of diseases associated with adiposity. We aimed to identify consistent protein signatures of weight loss across independent studies capturing changes in body mass index (BMI). We analysed proteomic data from studies implementing caloric restriction (Diabetes Remission Clinical trial) and bariatric surgery (By-Band-Sleeve), using SomaLogic and Olink Explore1536 technologies, respectively. Linear mixed models were used to estimate the effect of the interventions on circulating proteins. Twenty-three proteins were altered in a consistent direction after both bariatric surgery and caloric restriction, suggesting that these proteins are modulated by weight change, independent of intervention type. We also integrated Mendelian randomisation (MR) estimates of the effect of BMI on proteins measured by SomaLogic from a UK blood donor cohort as a third line of causal evidence. These MR estimates provided further corroborative evidence for a role of BMI in regulating the levels of six proteins including alcohol dehydrogenase-4, nogo receptor and interleukin-1 receptor antagonist protein. These results indicate the importance of triangulation in interrogating causal relationships; further study into the role of proteins modulated by weight in disease is now warranted.

U2 - 10.1038/s41598-023-47030-x

DO - 10.1038/s41598-023-47030-x

M3 - Article (Academic Journal)

C2 - 38030643

SN - 2045-2322

VL - 13

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 21077

ER -

Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome

Abstract

Bibliographical note

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Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

Gastric Bypass, adjustable gastric Banding or Sleeve gastorectomy surgery to treat severe and complex obesity: a multi-centre randomised controlled trial (The By-Band Sleeve Study) HTA Project No. 09/127/53

Cite this