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Updated: Jul 12, 2025
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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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GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity
Xue-Nan Sun1, Yu A An1,2, Vivian A Paschoal1
1Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
The Journal of Clinical Investigation
|October 19, 2023
Summary
G protein-coupled receptor 84 (GPR84) plays a key role in brown adipose tissue (BAT) activity. Its deficiency impairs mitochondrial function, leading to metabolic issues, but GPR84 activation may offer therapeutic potential.
Area of Science:
- Metabolic research
- Adipose tissue biology
- Mitochondrial function
Background:
- G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, is implicated in metabolic conditions.
- The specific role and mechanisms of GPR84 in metabolic regulation are not fully understood.
Purpose of the Study:
- To investigate the role of GPR84 in brown adipose tissue (BAT) function.
- To elucidate the mechanisms by which GPR84 influences BAT activity and energy metabolism.
Main Methods:
- Utilized GPR84 knockout (GPR84-KO) mice and wild-type (WT) littermates.
- Performed in vitro studies using primary brown adipocytes.
- Assessed BAT lipid accumulation, thermogenic gene expression, oxygen consumption, and intracellular calcium levels.
- Administered a GPR84 agonist (6-n-octylaminouracil, 6-OAU).
Main Results:
- GPR84-KO mice showed increased BAT lipid accumulation, reduced BAT activity, and heightened susceptibility to cold.
- Primary brown adipocytes from GPR84-KO mice exhibited diminished thermogenic gene expression and reduced oxygen consumption.
- GPR84 agonist (6-OAU) treatment restored brown adipocyte activity in vitro.
- GPR84 activation increased intracellular Ca2+ levels, influencing mitochondrial respiration.
Conclusions:
- GPR84 is robustly expressed and functionally significant in brown adipose tissue.
- Mitochondrial dysfunction underlies BAT anomalies in GPR84-deficient mice.
- GPR84 modulates mitochondrial Ca2+ levels and respiration, impacting BAT activity.
- GPR84 represents a potential therapeutic target for metabolic disorders.
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