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

Authors :
Yu X
Benitez G
Wei PT
Krylova SV
Song Z
Liu L
Zhang M
Xiaoli AM
Wei H
Chen F
Sidoli S
Yang F
Shinoda K
Pessin JE
Feng D
Source :
Nature communications [Nat Commun] 2024 Apr 02; Vol. 15 (1), pp. 2856. Date of Electronic Publication: 2024 Apr 02.
Publication Year :
2024

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.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
2041-1723
Volume :
15
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
38565851
Full Text :
https://doi.org/10.1038/s41467-024-46944-y