IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27289-2.html
   My bibliography  Save this article

High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control

Author

Listed:
  • Jonathan M. Dreyfuss

    (Joslin Diabetes Center
    Boston University
    Harvard Medical School)

  • Yixing Yuchi

    (Harvard Medical School
    Joslin Diabetes Center
    Vertex Pharmaceuticals)

  • Xuehong Dong

    (Harvard Medical School
    Joslin Diabetes Center
    Zhejiang University School of Medicine)

  • Vissarion Efthymiou

    (Harvard Medical School
    Joslin Diabetes Center)

  • Hui Pan

    (Joslin Diabetes Center
    Boston University)

  • Donald C. Simonson

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Ashley Vernon

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Florencia Halperin

    (Harvard Medical School
    Brigham and Women’s Hospital
    Form Health)

  • Pratik Aryal

    (Harvard Medical School
    Beth Israel Deaconess Medical Center)

  • Anish Konkar

    (MedImmune
    Eli Lilly and Company)

  • Yinong Sebastian

    (MedImmune)

  • Brandon W. Higgs

    (MedImmune
    Genmab)

  • Joseph Grimsby

    (MedImmune
    AstraZeneca)

  • Cristina M. Rondinone

    (MedImmune)

  • Simon Kasif

    (Boston University)

  • Barbara B. Kahn

    (Harvard Medical School
    Beth Israel Deaconess Medical Center)

  • Kathleen Foster

    (Joslin Diabetes Center)

  • Randy Seeley

    (University of Michigan)

  • Allison Goldfine

    (Harvard Medical School
    Joslin Diabetes Center
    Brigham and Women’s Hospital
    Novartis Institute for Biomedical Research)

  • Vera Djordjilović

    (Ca’ Foscari University of Venice)

  • Mary Elizabeth Patti

    (Harvard Medical School
    Joslin Diabetes Center)

Abstract

To improve the power of mediation in high-throughput studies, here we introduce High-throughput mediation analysis (Hitman), which accounts for direction of mediation and applies empirical Bayesian linear modeling. We apply Hitman in a retrospective, exploratory analysis of the SLIMM-T2D clinical trial in which participants with type 2 diabetes were randomized to Roux-en-Y gastric bypass (RYGB) or nonsurgical diabetes/weight management, and fasting plasma proteome and metabolome were assayed up to 3 years. RYGB caused greater improvement in HbA1c, which was mediated by growth hormone receptor (GHR). GHR’s mediation is more significant than clinical mediators, including BMI. GHR decreases at 3 months postoperatively alongside increased insulin-like growth factor binding proteins IGFBP1/BP2; plasma GH increased at 1 year. Experimental validation indicates (1) hepatic GHR expression decreases in post-bariatric rats; (2) GHR knockdown in primary hepatocytes decreases gluconeogenic gene expression and glucose production. Thus, RYGB may induce resistance to diabetogenic effects of GH signaling. Trial Registration: Clinicaltrials.gov NCT01073020.

Suggested Citation

  • Jonathan M. Dreyfuss & Yixing Yuchi & Xuehong Dong & Vissarion Efthymiou & Hui Pan & Donald C. Simonson & Ashley Vernon & Florencia Halperin & Pratik Aryal & Anish Konkar & Yinong Sebastian & Brandon , 2021. "High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27289-2
    DOI: 10.1038/s41467-021-27289-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27289-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-27289-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Cho, Hyun-Chul & Abe, Shuzo, 2013. "Is two-tailed testing for directional research hypotheses tests legitimate?," Journal of Business Research, Elsevier, vol. 66(9), pages 1261-1266.
    2. Qin Yang & Timothy E. Graham & Nimesh Mody & Frederic Preitner & Odile D. Peroni & Janice M. Zabolotny & Ko Kotani & Loredana Quadro & Barbara B. Kahn, 2005. "Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes," Nature, Nature, vol. 436(7049), pages 356-362, July.
    3. Karen K. Ryan & Valentina Tremaroli & Christoffer Clemmensen & Petia Kovatcheva-Datchary & Andriy Myronovych & Rebekah Karns & Hilary E. Wilson-Pérez & Darleen A. Sandoval & Rohit Kohli & Fredrik Bäck, 2014. "FXR is a molecular target for the effects of vertical sleeve gastrectomy," Nature, Nature, vol. 509(7499), pages 183-188, May.
    4. Jeffrey T Leek & John D Storey, 2007. "Capturing Heterogeneity in Gene Expression Studies by Surrogate Variable Analysis," PLOS Genetics, Public Library of Science, vol. 3(9), pages 1-12, September.
    5. Tingley, Dustin & Yamamoto, Teppei & Hirose, Kentaro & Keele, Luke & Imai, Kosuke, 2014. "mediation: R Package for Causal Mediation Analysis," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 59(i05).
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Hirofumi Nagao & Ashok Kumar Jayavelu & Weikang Cai & Hui Pan & Jonathan M. Dreyfuss & Thiago M. Batista & Bruna B. Brandão & Matthias Mann & C. Ronald Kahn, 2023. "Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Atanasov, Pavel & Witkowski, Jens & Ungar, Lyle & Mellers, Barbara & Tetlock, Philip, 2020. "Small steps to accuracy: Incremental belief updaters are better forecasters," Organizational Behavior and Human Decision Processes, Elsevier, vol. 160(C), pages 19-35.
    3. Shengkui Zhang & Yongbin Wang & Ying Zhu & Xiaoming Li & Yang Song & Juxiang Yuan, 2020. "Rotating Night Shift Work, Exposure to Light at Night, and Glomerular Filtration Rate: Baseline Results from a Chinese Occupational Cohort," IJERPH, MDPI, vol. 17(23), pages 1-14, December.
    4. Antonio R. Linero, 2022. "Simulation‐based estimators of analytically intractable causal effects," Biometrics, The International Biometric Society, vol. 78(3), pages 1001-1017, September.
    5. Shengkui Zhang & Han Wang & Yongbin Wang & Miao Yu & Juxiang Yuan, 2021. "Association of Rotating Night Shift Work with Body Fat Percentage and Fat Mass Index among Female Steelworkers in North China," IJERPH, MDPI, vol. 18(12), pages 1-15, June.
    6. Martin Huber & Yu‐Chin Hsu & Ying‐Ying Lee & Layal Lettry, 2020. "Direct and indirect effects of continuous treatments based on generalized propensity score weighting," Journal of Applied Econometrics, John Wiley & Sons, Ltd., vol. 35(7), pages 814-840, November.
    7. Effron, Daniel A. & Raj, Medha, 2021. "Disclosing interpersonal conflicts of interest: Revealing whom we like, but not whom we dislike," Organizational Behavior and Human Decision Processes, Elsevier, vol. 164(C), pages 68-85.
    8. Vonneilich, Nico & Lüdecke, Daniel & von dem Knesebeck, Olaf, 2020. "Educational inequalities in self-rated health and social relationships – analyses based on the European Social Survey 2002-2016," Social Science & Medicine, Elsevier, vol. 267(C).
    9. Pascal Paillé & Jorge H. Mejía Morelos & Nicolas Raineri & Florence Stinglhamber, 2019. "The Influence of the Immediate Manager on the Avoidance of Non-green Behaviors in the Workplace: A Three-Wave Moderated-Mediation Model," Journal of Business Ethics, Springer, vol. 155(3), pages 723-740, March.
    10. Erin Percival Carter & Stephanie Welcomer, 2021. "Designing and Distinguishing Meaningful Artisan Food Experiences," Sustainability, MDPI, vol. 13(15), pages 1-13, July.
    11. A. Q. Adeleke & A. Y. Bahaudin & A. M. Kamaruddeen, 2018. "Organizational Internal Factors and Construction Risk Management among Nigerian Construction Companies," Global Business Review, International Management Institute, vol. 19(4), pages 921-938, August.
    12. Sato, Yukihiro & Aida, Jun & Tsuboya, Toru & Shirai, Kokoro & Koyama, Shihoko & Matsuyama, Yusuke & Kondo, Katsunori & Osaka, Ken, 2018. "Generalized and particularized trust for health between urban and rural residents in Japan: A cohort study from the JAGES project," Social Science & Medicine, Elsevier, vol. 202(C), pages 43-53.
    13. Arjun Bhattacharya & Anastasia N. Freedman & Vennela Avula & Rebeca Harris & Weifang Liu & Calvin Pan & Aldons J. Lusis & Robert M. Joseph & Lisa Smeester & Hadley J. Hartwell & Karl C. K. Kuban & Car, 2022. "Placental genomics mediates genetic associations with complex health traits and disease," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Daniel Roos & Rüdiger Hahn, 2019. "Understanding Collaborative Consumption: An Extension of the Theory of Planned Behavior with Value-Based Personal Norms," Journal of Business Ethics, Springer, vol. 158(3), pages 679-697, September.
    15. Stinshoff, Volker, 2020. "Selbst gemacht ist gut gemacht? Der Einfluss von Self-Service Reporting auf die Qualität von Managemententscheidungen," Junior Management Science (JUMS), Junior Management Science e. V., vol. 5(2), pages 223-245.
    16. Lara Lopez & Fernando L. Vázquez & Ángela J. Torres & Patricia Otero & Vanessa Blanco & Olga Díaz & Mario Páramo, 2020. "Long-Term Effects of a Cognitive Behavioral Conference Call Intervention on Depression in Non-Professional Caregivers," IJERPH, MDPI, vol. 17(22), pages 1-24, November.
    17. Francesco Sartor & Jonathan P. Moore & Hans-Peter Kubis, 2021. "Plasma Interleukin-10 and Cholesterol Levels May Inform about Interdependences between Fitness and Fatness in Healthy Individuals," IJERPH, MDPI, vol. 18(4), pages 1-19, February.
    18. Lee, Anthony J. & Hibbs, Courtney & Wright, Margaret J. & Martin, Nicholas G. & Keller, Matthew C. & Zietsch, Brendan P., 2017. "Assessing the accuracy of perceptions of intelligence based on heritable facial features," Intelligence, Elsevier, vol. 64(C), pages 1-8.
    19. Schuessler, Julian, 2024. "Causal analysis with observational data," OSF Preprints wam94, Center for Open Science.
    20. Josef Ringqvist, 2022. "Union membership and the willingness to prioritize environmental protection above growth and jobs: A multi‐level analysis covering 22 European countries," British Journal of Industrial Relations, London School of Economics, vol. 60(3), pages 662-682, September.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27289-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.