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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Tumor-necrosis-factor; Fatty Liver-disease; Signal-related Kinase; Factor-alpha; Insulin-resistance; Induced Obesity; Brown Fat; Metabolic Syndrome; Hepatic Steatosis; April Expression
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2021
Prepublished im Jahr
HGF-Berichtsjahr
2021
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 12,
Heft: 1,
Seiten: ,
Artikelnummer: 2911
Supplement: ,
Reihe
Verlag
Nature Publishing Group
Verlagsort
London
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30201 - Metabolic Health
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502294-001
G-502200-001
Förderungen
NIDDK NIH HHS
NIGMS NIH HHS
NIAID NIH HHS
Copyright
Erfassungsdatum
2021-06-28