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A BAFF/APRIL axis regulates obesogenic diet-driven weight gain by Chan, Calvin C. (author);Harley, Isaac T. W. (author);Pfluger, Paul T. (author);Trompette, Aurelien (author);Stankiewicz, Traci E. (author);Allen, Jessica L. (author);Moreno-Fernandez, Maria E. (author);Damen, Michelle S. M. A. (author);Oates, Jarren R. (author);Alarcon, Pablo C. (author);Doll, Jessica R. (author);Flick, Matthew J. (author);Flick, Leah M. (author);Sanchez-Gurmaches, Joan (author);Mukherjee, Rajib (author);Karns, Rebekah (author);Helmrath, Michael (author);Inge, Thomas H. (author);Weisberg, Stuart P. (author);Pamp, Sünje J. (author);Relman, David A. (author);Seeley, Randy J. (author);Tschöp, Matthias H. (author);Karp, Christopher L. (author);Divanovic, Senad (author) is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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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 o

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Author

Chan, Calvin C. (author);Harley, Isaac T. W. (author);Pfluger, Paul T. (author);Trompette, Aurelien (author);Stankiewicz, Traci E. (author);Allen, Jessica L. (author);Moreno-Fernandez, Maria E. (author);Damen, Michelle S. M. A. (author);Oates, Jarren R. (author);Alarcon, Pablo C. (author);Doll, Jessica R. (author);Flick, Matthew J. (author);Flick, Leah M. (author);Sanchez-Gurmaches, Joan (author);Mukherjee, Rajib (author);Karns, Rebekah (author);Helmrath, Michael (author);Inge, Thomas H. (author);Weisberg, Stuart P. (author);Pamp, Sünje J. (author);Relman, David A. (author);Seeley, Randy J. (author);Tschöp, Matthias H. (author);Karp, Christopher L. (author);Divanovic, Senad (author)

Publisher

Springer Science and Business Media LLC

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)