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GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity.

Publication ,  Journal Article
Sun, X-N; An, YA; Paschoal, VA; de Souza, CO; Wang, M-Y; Vishvanath, L; Bueno, LM; Cobb, AS; Nieto Carrion, JA; Ibe, ME; Li, C; Kidd, HA ...
Published in: J Clin Invest
December 15, 2023

The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation in BAT, rendering them more susceptible to cold exposure and displaying reduced BAT activity compared with their WT counterparts. Our in vitro experiments with primary brown adipocytes from GPR84-KO mice revealed diminished expression of thermogenic genes and reduced O2 consumption. Furthermore, the application of the GPR84 agonist 6-n-octylaminouracil (6-OAU) counteracted these effects, effectively reinstating the brown adipocyte activity. These compelling in vivo and in vitro findings converge to highlight mitochondrial dysfunction as the primary cause of BAT anomalies in GPR84-KO mice. The activation of GPR84 induced an increase in intracellular Ca2+ levels, which intricately influenced mitochondrial respiration. By modulating mitochondrial Ca2+ levels and respiration, GPR84 acts as a potent molecule involved in BAT activity. These findings suggest that GPR84 is a potential therapeutic target for invigorating BAT and ameliorating metabolic disorders.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

December 15, 2023

Volume

133

Issue

24

Location

United States

Related Subject Headings

  • Thermogenesis
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • Mitochondria
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Fatty Acids
  • Calcium
  • Animals
 

Citation

APA
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MLA
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Sun, X.-N., An, Y. A., Paschoal, V. A., de Souza, C. O., Wang, M.-Y., Vishvanath, L., … Oh, D. Y. (2023). GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity. J Clin Invest, 133(24). https://doi.org/10.1172/JCI168992
Sun, Xue-Nan, Yu A. An, Vivian A. Paschoal, Camila O. de Souza, May-Yun Wang, Lavanya Vishvanath, Lorena Ma Bueno, et al. “GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity.J Clin Invest 133, no. 24 (December 15, 2023). https://doi.org/10.1172/JCI168992.
Sun X-N, An YA, Paschoal VA, de Souza CO, Wang M-Y, Vishvanath L, et al. GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity. J Clin Invest. 2023 Dec 15;133(24).
Sun, Xue-Nan, et al. “GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity.J Clin Invest, vol. 133, no. 24, Dec. 2023. Pubmed, doi:10.1172/JCI168992.
Sun X-N, An YA, Paschoal VA, de Souza CO, Wang M-Y, Vishvanath L, Bueno LM, Cobb AS, Nieto Carrion JA, Ibe ME, Li C, Kidd HA, Chen S, Li W, Gupta RK, Oh DY. GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity. J Clin Invest. 2023 Dec 15;133(24).

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

December 15, 2023

Volume

133

Issue

24

Location

United States

Related Subject Headings

  • Thermogenesis
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • Mitochondria
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Fatty Acids
  • Calcium
  • Animals