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A BAFF/APRIL axis regulates obesogenic diet-driven weight gain

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  • Calvin C. Chan

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center
    Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center)

  • Isaac T. W. Harley

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center
    Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center)

  • Paul T. Pfluger

    (Helmholtz Center Munich
    Helmholtz Center Munich
    German Center for Diabetes Research (DZD)
    Technische Universität München)

  • Aurelien Trompette

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    University of Lausanne, Service de Pneumologie, CHUV, CLED 02.206)

  • Traci E. Stankiewicz

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Jessica L. Allen

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center)

  • Maria E. Moreno-Fernandez

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Michelle S. M. A. Damen

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Jarren R. Oates

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center)

  • Pablo C. Alarcon

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center
    Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center)

  • Jessica R. Doll

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Matthew J. Flick

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    The University of North Carolina at Chapel Hill)

  • Leah M. Flick

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Joan Sanchez-Gurmaches

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Cincinnati Children’s Hospital Medical Center)

  • Rajib Mukherjee

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Rebekah Karns

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Michael Helmrath

    (Cincinnati Children’s Hospital Medical Center
    Cincinnati Children’s Hospital Medical Center)

  • Thomas H. Inge

    (Children’s Hospital Colorado)

  • Stuart P. Weisberg

    (Columbia University Medical Center)

  • Sünje J. Pamp

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Technical University of Denmark)

  • David A. Relman

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Veterans Affairs Palo Alto Health Care System)

  • Randy J. Seeley

    (University of Michigan)

  • Matthias H. Tschöp

    (Helmholtz Center Munich
    German Center for Diabetes Research (DZD)
    Technische Universität München)

  • Christopher L. Karp

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center
    Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center)

  • Senad Divanovic

    (The University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Medical Scientist Training Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center
    Immunology Graduate Program, The University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center)

Abstract

The impact of immune mediators on weight homeostasis remains underdefined. Interrogation of resistance to diet-induced obesity in mice lacking a negative regulator of Toll-like receptor signaling serendipitously uncovered a role for B cell activating factor (BAFF). Here we show that overexpression of BAFF in multiple mouse models associates with protection from weight gain, approximating a log-linear dose response relation to BAFF concentrations. Gene expression analysis of BAFF-stimulated subcutaneous white adipocytes unveils upregulation of lipid metabolism pathways, with BAFF inducing white adipose tissue (WAT) lipolysis. Brown adipose tissue (BAT) from BAFF-overexpressing mice exhibits increased Ucp1 expression and BAFF promotes brown adipocyte respiration and in vivo energy expenditure. A proliferation-inducing ligand (APRIL), a BAFF homolog, similarly modulates WAT and BAT lipid handling. Genetic deletion of both BAFF and APRIL augments diet-induced obesity. Lastly, BAFF/APRIL effects are conserved in human adipocytes and higher BAFF/APRIL levels correlate with greater BMI decrease after bariatric surgery. Together, the BAFF/APRIL axis is a multifaceted immune regulator of weight gain and adipose tissue function.

Suggested Citation

  • Calvin C. Chan & Isaac T. W. Harley & Paul T. Pfluger & Aurelien Trompette & Traci E. Stankiewicz & Jessica L. Allen & Maria E. Moreno-Fernandez & Michelle S. M. A. Damen & Jarren R. Oates & Pablo C. , 2021. "A BAFF/APRIL axis regulates obesogenic diet-driven weight gain," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23084-1
    DOI: 10.1038/s41467-021-23084-1
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