The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- e8047.full
Final published version, 3.15 MB, PDF document
Brown adipose tissue (BAT) activation stimulates energy expenditure in human adults, which makes it an attractive target to combat obesity and related disorders. Recent studies demonstrated a role for G protein-coupled receptor 120 (GPR120) in BAT thermogenesis. Here, we investigated the therapeutic potential of GPR120 agonism and addressed GPR120-mediated signaling in BAT We found that activation of GPR120 by the selective agonist TUG-891 acutely increases fat oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects coincided with decreased brown adipocyte lipid content and increased nutrient uptake by BAT, confirming increased BAT activity. Consistent with these observations, GPR120 deficiency reduced expression of genes involved in nutrient handling in BAT Stimulation of brown adipocytes in vitro with TUG-891 acutely induced O2 consumption, through GPR120-dependent and GPR120-independent mechanisms. TUG-891 not only stimulated GPR120 signaling resulting in intracellular calcium release, mitochondrial depolarization, and mitochondrial fission, but also activated UCP1. Collectively, these data suggest that activation of brown adipocytes with the GPR120 agonist TUG-891 is a promising strategy to increase lipid combustion and reduce obesity.
Original language | English |
---|---|
Article number | e8047 |
Journal | E M B O Molecular Medicine |
Volume | 10 |
Issue number | 3 |
Number of pages | 18 |
ISSN | 1757-4676 |
DOIs | |
Publication status | Published - 17 Jan 2018 |
Externally published | Yes |
Bibliographical note
© 2018 The Authors. Published under the terms of the CC BY 4.0 license.
- Journal Article
Research areas
Number of downloads are based on statistics from Google Scholar and www.ku.dk
No data available
ID: 189159353