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SYK kinase mediates brown fat differentiation and activation

Author(s)
Knoll, Marko; Winther, Sally; Natarajan, Anirudh; Yang, Huan; Jiang, Mengxi; Thiru, Prathapan; Shahsafaei, Aliakbar; Chavarria, Tony E.; Lamming, Dudley W.; Sun, Lei; Hansen, Jacob B.; Lodish, Harvey F; ... Show more Show less
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Abstract
Brown adipose tissue (BAT) metabolism influences glucose homeostasis and metabolic health in mice and humans. Sympathetic stimulation of β-adrenergic receptors in response to cold induces proliferation, differentiation, and UCP1 expression in pre-adipocytes and mature brown adipocytes. Here we show that spleen tyrosine kinase (SYK) is upregulated during brown adipocyte differentiation and activated by β-adrenergic stimulation. Deletion or inhibition of SYK, a kinase known for its essential roles in the immune system, blocks brown and white pre-adipocyte proliferation and differentiation in vitro, and results in diminished expression of Ucp1 and other genes regulating brown adipocyte function in response to β-adrenergic stimulation. Adipocyte-specific SYK deletion in mice reduces BAT mass and BAT that developed consisted of SYK-expressing brown adipocytes that had escaped homozygous Syk deletion. SYK inhibition in vivo represses β-agonist-induced thermogenesis and oxygen consumption. These results establish SYK as an essential mediator of brown fat formation and function.
Date issued
2017-12
URI
http://hdl.handle.net/1721.1/113618
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Knoll, Marko et al. “SYK Kinase Mediates Brown Fat Differentiation and Activation.” Nature Communications 8, 1 (December 2017) © 2017 The Author(s)
Version: Final published version
ISSN
2041-1723

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