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Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
Published on: February 3, 2023
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Involution of brown adipose tissue through a Syntaxin 4 dependent pyroptosis pathway
Xiaofan Yu1,2, Gabrielle Benitez1,2, Peter Tszki Wei3
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Nature Communications
|April 2, 2024
Summary
Aging causes brown adipose tissue (BAT) loss. Restoring syntaxin 4 (STX4) or inhibiting pyroptosis prevents this decline, revealing a key mechanism in thermogenic dysfunction.
Area of Science:
- Metabolism
- Cell Biology
- Aging Research
Background:
- Brown adipose tissue (BAT) involution, marked by reduced mass and function, occurs with aging, high-fat diets, or thermoneutral housing.
- This involution involves increased lipid droplet size and a specific Ucp1-low brown adipocyte population exhibiting pyroptosis and reduced syntaxin 4 (STX4).
Purpose of the Study:
- To investigate the role of STX4 and pyroptosis in brown adipose tissue involution during aging and thermogenic dysfunction.
- To identify mechanisms linking STX4 deficiency to impaired BAT function and pyroptosis.
Main Methods:
- Single nuclei RNA sequencing of aged mouse BAT.
- Genetic manipulation (Ucp1-STX4KO mice) to study STX4 deficiency.
- Assessment of BAT mass, thermogenic activity, pyroptosis markers, and metabolic pathways (oxidative phosphorylation, glucose uptake, glycolysis).
Main Results:
- Aged brown adipocytes and Ucp1-STX4KO mice exhibit reduced BAT mass, thermogenic dysfunction, and increased pyroptosis.
- Restoring STX4 expression or suppressing pyroptosis ameliorates age-related BAT decline and dysfunction.
- STX4 deficiency impairs oxidative phosphorylation, glucose uptake, and glycolysis, leading to decreased ATP levels and triggering pyroptosis.
Conclusions:
- Physiological aging and thermogenic dysfunction are driven by pyroptotic signaling activation in brown adipocytes.
- STX4 plays a crucial role in maintaining BAT mass and function, and its deficiency promotes involution via pyroptosis.
- Targeting pyroptosis or restoring STX4 offers potential therapeutic strategies for age-related metabolic decline.
![Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62460.jpg&w=3840&q=50)
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