We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.
- Authors
Chan, Calvin C.; Harley, Isaac T. W.; Pfluger, Paul T.; Trompette, Aurelien; Stankiewicz, Traci E.; Allen, Jessica L.; Moreno-Fernandez, Maria E.; Damen, Michelle S. M. A.; Oates, Jarren R.; Alarcon, Pablo C.; Doll, Jessica R.; Flick, Matthew J.; Flick, Leah M.; Sanchez-Gurmaches, Joan; Mukherjee, Rajib; Karns, Rebekah; Helmrath, Michael; Inge, Thomas H.; Weisberg, Stuart P.; Pamp, Sünje J.
- 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. Interactions between the immune system and adipose tissue contribute to the regulation of body weight, however, the underlying mechanisms remain incompletely understood. Here the authors dissect the role of two structurally and functionally similar immune mediators, BAFF and APRIL, in modifying diet-induced weight gain and adipocyte lipid handling.
- Subjects
WEIGHT gain; WHITE adipose tissue; BROWN adipose tissue; REGULATION of body weight; LIPID metabolism; ADIPOSE tissues
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-23084-1