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

Autor: Maria E. Moreno-Fernandez, Michelle S M A Damen, Isaac T.W. Harley, Joan Sanchez-Gurmaches, David A. Relman, Stuart P. Weisberg, Pablo C Alarcon, Matthew J. Flick, Matthias H. Tschöp, Calvin C. Chan, Aurelien Trompette, Rajib Mukherjee, Christopher L. Karp, Randy J. Seeley, Traci E. Stankiewicz, Leah M. Flick, Paul T. Pfluger, Jessica R Doll, Sünje Johanna Pamp, Michael A. Helmrath, Senad Divanovic, Thomas H. Inge, Jarren R Oates, Jessica L. Allen, Rebekah Karns
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
General Physics and Astronomy
Adipose tissue
White adipose tissue
Weight Gain
0302 clinical medicine
Adipose Tissue
Brown
immune system diseases
hemic and lymphatic diseases
B-Cell Activating Factor
Brown adipose tissue
Adipocytes
skin and connective tissue diseases
Cells
Cultured
Mice
Knockout
Multidisciplinary
medicine.anatomical_structure
Cytokines
Signal Transduction
medicine.medical_specialty
Science
Adipose Tissue
White
Tumor Necrosis Factor Ligand Superfamily Member 13
Mice
Transgenic
Biology
Diet
High-Fat
Article
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
SDG 3 - Good Health and Well-being
stomatognathic system
Downregulation and upregulation
Internal medicine
medicine
Animals
Humans
Lipolysis
Obesity
B-cell activating factor
Gene Expression Profiling
Lipid metabolism
General Chemistry
Mice
Inbred C57BL
stomatognathic diseases
030104 developmental biology
Endocrinology
030217 neurology & neurosurgery
Homeostasis
Zdroj: Nature Communications
Chan, C C, Harley, I T W, 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, Tschöp, M H, Karp, C L & Divanovic, S 2021, ' A BAFF/APRIL axis regulates obesogenic diet-driven weight gain ', Nature Communications, vol. 12, no. 1, 2911 . https://doi.org/10.1038/s41467-021-23084-1
Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
Nat. Commun. 12:2911 (2021)
ISSN: 2041-1723
Popis: 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.
Databáze: OpenAIRE
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