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Involution of brown adipose tissue through a Syntaxin 4 dependent pyroptosis pathway.

Citation
Yu, X., et al. “Involution Of Brown Adipose Tissue Through A Syntaxin 4 Dependent Pyroptosis Pathway.”. Nature Communications, p. 2856.
Center Albert Einstein College of Medicine
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Author Xiaofan Yu, Gabrielle Benitez, Peter Tszki Wei, Sofia Krylova V, Ziyi Song, Li Liu, Meifan Zhang, Alus M Xiaoli, Henna Wei, Fenfen Chen, Simone Sidoli
Abstract

Aging, chronic high-fat diet feeding, or housing at thermoneutrality induces brown adipose tissue (BAT) involution, a process characterized by reduction of BAT mass and function with increased lipid droplet size. Single nuclei RNA sequencing of aged mice identifies a specific brown adipocyte population of Ucp1-low cells that are pyroptotic and display a reduction in the longevity gene syntaxin 4 (Stx4a). Similar to aged brown adipocytes, Ucp1-STX4KO mice display loss of brown adipose tissue mass and thermogenic dysfunction concomitant with increased pyroptosis. Restoration of STX4 expression or suppression of pyroptosis activation protects against the decline in both mass and thermogenic activity in the aged and Ucp1-STX4KO mice. Mechanistically, STX4 deficiency reduces oxidative phosphorylation, glucose uptake, and glycolysis leading to reduced ATP levels, a known triggering signal for pyroptosis. Together, these data demonstrate an understanding of rapid brown adipocyte involution and that physiologic aging and thermogenic dysfunction result from pyroptotic signaling activation.

Year of Publication
2024
Journal
Nature communications
Volume
15
Issue
1
Number of Pages
2856
Date Published
04/2024
ISSN Number
2041-1723
DOI
10.1038/s41467-024-46944-y
Alternate Journal
Nat Commun
PMID
38565851
PMCID
PMC10987578
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