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

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. Alarcon, Jessica R. Doll, Matthew J. Flick, Leah M. Flick, Joan Sanchez-Gurmaches, Rajib Mukherjee, Rebekah Karns, Michael Helmrath, Thomas H. Inge, Stuart P. Weisberg, Sünje J. Pamp, David A. Relman, Randy J. Seeley, Matthias H. Tschöp, Christopher L. Karp and Senad Divanovic ()
Additional contact information
Calvin C. Chan: The University of Cincinnati College of Medicine
Isaac T. W. Harley: The University of Cincinnati College of Medicine
Paul T. Pfluger: Helmholtz Center Munich
Aurelien Trompette: The University of Cincinnati College of Medicine
Traci E. Stankiewicz: The University of Cincinnati College of Medicine
Jessica L. Allen: The University of Cincinnati College of Medicine
Maria E. Moreno-Fernandez: The University of Cincinnati College of Medicine
Michelle S. M. A. Damen: The University of Cincinnati College of Medicine
Jarren R. Oates: The University of Cincinnati College of Medicine
Pablo C. Alarcon: The University of Cincinnati College of Medicine
Jessica R. Doll: The University of Cincinnati College of Medicine
Matthew J. Flick: The University of Cincinnati College of Medicine
Leah M. Flick: The University of Cincinnati College of Medicine
Joan Sanchez-Gurmaches: The University of Cincinnati College of Medicine
Rajib Mukherjee: The University of Cincinnati College of Medicine
Rebekah Karns: The University of Cincinnati College of Medicine
Michael Helmrath: 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
David A. Relman: Stanford University School of Medicine
Randy J. Seeley: University of Michigan
Matthias H. Tschöp: Helmholtz Center Munich
Christopher L. Karp: The University of Cincinnati College of Medicine
Senad Divanovic: The University of Cincinnati College of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23084-1

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