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Chan, C.C.* ; Pfluger, P.T. ; Trompette, A.* ; Stankiewicz, T.E.* ; Allen, J.L.* ; Moreno-Fernandez, M.E.* ; Damen, M.S.M.A.* ; Oates, J.R.* ; Alarcon, P.C.* ; Doll, J.R.* ; Flick, M.J.* ; Flick, L.M.* ; Sanchez-Gurmaches, J.* ; Mukherjee, R.* ; Karns, R.* ; Helmrath, M.* ; Inge, T.H.* ; Weisberg, S.P.* ; Pamp, S.J.* ; Relman, D.A.* ; Seeley, R.J.* ; Karp, C.L. ; Divanovic, S.*

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

Nat. Commun. 12:2911 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Tumor-necrosis-factor; Fatty Liver-disease; Signal-related Kinase; Factor-alpha; Insulin-resistance; Induced Obesity; Brown Fat; Metabolic Syndrome; Hepatic Steatosis; April Expression
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 12, Issue: 1, Pages: , Article Number: 2911 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Grants NIDDK NIH HHS
NIGMS NIH HHS
NIAID NIH HHS